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HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
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USD 80+
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Structure of 148-24-3 * Storage: {[proInfo.prStorage]}
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With bromine In chloroform at 20℃; for 48 h; Darkness
General procedure: To synthesize brominated 8-substituted quinolines (5-10) experimental procedures were repeated in literature [19]. In brief, to a solution of 8-substituted quinoline 2-4 (2 mmol, 1 eq) in distilled CHCl3 (15 mL) was added a solution of molecular bromine (different eqivalents) in CHCl3 over 10 min in the dark at ambient temperature and stirred for 2 days. The reaction was monitored by TLC; after completion of the reaction, the organic layer was washed with 5percent NaHCO3 (3 × 20 mL), dried over Na2SO4, and concentrated under reduced pressure. The products was isolated by alumina column, eluting with AcOEt/hexane (1:5, 150 mL).
Reference：
[1] Letters in Drug Design and Discovery, 2017, vol. 14, # 12, p. 1415 - 1424
Reference：
[1] Chemical Science, 2018, vol. 9, # 7, p. 1782 - 1788
[2] Journal of the Indian Chemical Society, 1945, vol. 22, p. 171
6
[ 56-81-5 ]
[ 88-75-5 ]
[ 148-24-3 ]
[ 130-16-5 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1947, p. 969
[2] Roczniki Chemii, 1936, vol. 16, p. 519,522[3] Chem. Zentralbl., 1937, vol. 108, # I, p. 3142
7
[ 148-24-3 ]
[ 130-16-5 ]
Reference：
[1] Chemische Berichte, 1919, vol. 52, p. 193
[2] Acta Pharmaceutica Internationalia, 1951, vol. 2, p. 149,154
Reference：
[1] Journal of the Chemical Society, Chemical Communications, 1987, p. 1722 - 1724
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 9, p. 1065 - 1072
[3] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 9, p. 1065 - 1072
10
[ 91-22-5 ]
[ 580-18-7 ]
[ 148-24-3 ]
[ 112259-26-4 ]
[ 141977-87-9 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 9, p. 1065 - 1072
11
[ 91-22-5 ]
[ 580-18-7 ]
[ 148-24-3 ]
[ 118-92-3 ]
[ 112259-26-4 ]
[ 141977-87-9 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 9, p. 1065 - 1072
12
[ 91-22-5 ]
[ 148-24-3 ]
[ 578-67-6 ]
[ 10470-83-4 ]
[ 59-31-4 ]
[ 529-37-3 ]
[ 529-23-7 ]
Reference：
[1] Journal of Physical Chemistry B, 1997, vol. 101, # 14, p. 2650 - 2658
13
[ 148-24-3 ]
[ 394-68-3 ]
Reference：
[1] Journal of the American Chemical Society, 2011, vol. 133, # 30, p. 11482 - 11484
[2] Patent: WO2012/142162, 2012, A2, . Location in patent: Page/Page column 24
[3] Organic Letters, 2015, vol. 17, # 3, p. 544 - 547
[4] Journal of the American Chemical Society, 2017, vol. 139, # 4, p. 1452 - 1455
[5] Journal of the American Chemical Society, 2017, vol. 139, # 4, p. 1452 - 1455
14
[ 148-24-3 ]
[ 10470-83-4 ]
Yield
Reaction Conditions
Operation in experiment
44%
With potassium dihydrogenphosphate; Fremy's salt In water; acetone at 20℃; for 3.16667 h;
Example 2.1: Procedure for the Preparation of the Starting Materials; Typically a solution of Fremy's salt (1 g, 4 mmol) and potassium dihydrogenphosphate (400 mg, 3 mmol) in water (75 ml) was stirred at room temperature for 10 min then the quinolinol (6 mmol) in acetone (70 ml) was added. The mixture was stirred for 30 min, then a further solution of Fremy's salt (1 g) and potassium dihydrogenphosphate (400 mg) in water (30 ml) was added and the mixture stirred for 30 min, then a further solution of Fremy's salt (1 g) and potassium dihydrogenphosphate (400 mg) in water (30 ml) was added and the mixture stirred for a further 2 h. The mixture was extracted into dichloromethane, dried and evaporated in vacuo to give the product as an orange gum. Purification by column chromatography over silica gel eluting with ethyl acetate (0 - 40percent ) in dichloromethane gave the products as orange solids.The following quinolines were prepared using this method; 5,8-Dihydro-5,8-dioxoquinoline (reg. no. 858471-89-3); 8-Hydroxyquinoline (1 g, 7 mmol) to give quinone (0.48 g, 44percent).
Reference：
[1] Australian Journal of Chemistry, 1982, vol. 35, # 7, p. 1439 - 1450
[2] Organic and Biomolecular Chemistry, 2008, vol. 6, # 15, p. 2731 - 2742
[3] Tetrahedron Letters, 2001, vol. 42, # 26, p. 4329 - 4331
[4] Synthetic Communications, 1999, vol. 29, # 18, p. 3063 - 3066
[5] Patent: WO2006/31134, 2006, A1, . Location in patent: Page/Page column 18-19
[6] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 21, p. 9432 - 9442
[7] Polish Journal of Chemistry, 1998, vol. 72, # 1, p. 122 - 126
[8] Chemische Berichte, 1954, vol. 87, p. 1236,1250
[9] Journal of Heterocyclic Chemistry, 2002, vol. 39, # 1, p. 125 - 130
[10] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1991, vol. 46, # 3, p. 326 - 338
[11] Journal of the Chemical Society, 1953, p. 3161,3166
[12] Tetrahedron Letters, 2013, vol. 54, # 24, p. 3147 - 3149
[13] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 17, p. 4609 - 4620
15
[ 75-91-2 ]
[ 148-24-3 ]
[ 10470-83-4 ]
[ 75-65-0 ]
Reference：
[1] Green Chemistry, 2010, vol. 12, # 6, p. 1076 - 1082
16
[ 75-91-2 ]
[ 148-24-3 ]
[ 10470-83-4 ]
[ 84288-96-0 ]
[ 75-65-0 ]
Reference：
[1] Green Chemistry, 2010, vol. 12, # 6, p. 1076 - 1082
17
[ 91-22-5 ]
[ 148-24-3 ]
[ 578-67-6 ]
[ 10470-83-4 ]
[ 59-31-4 ]
[ 529-37-3 ]
[ 529-23-7 ]
Reference：
[1] Journal of Physical Chemistry B, 1997, vol. 101, # 14, p. 2650 - 2658
18
[ 148-24-3 ]
[ 5541-67-3 ]
Reference：
[1] Helvetica Chimica Acta, 1956, vol. 39, p. 1676,1680
Reference：
[1] Monatshefte fuer Chemie, 1895, vol. 16, p. 761
[2] Chemistry and Industry (London, United Kingdom), 1957, p. 1271
21
[ 148-24-3 ]
[ 6640-50-2 ]
Yield
Reaction Conditions
Operation in experiment
95%
With hydrogen In water at 20℃; for 0.666667 h;
The 100mmol 8-hydroxy quinoline and load 0.7mmol catalyst polymer microspheres [...] Poly (DVB-co-NVP) Rh and 500 ml of water are added in a reaction kettle, to hydrogen replaces the cauldron five times the air in, and then filled with hydrogen, the reaction at normal temperature and pressure 40 minutes, the aqueous phase is extracted three times with ethyl ether, the merger ether level, ethyl ether evaporate after drying, to obtain 8-hydroxy -1, 2, 3, 4-tetrahydro-quinoline, yield 95percent.
93%
With sodium tetrahydroborate In ethanol; water at 60℃; for 3 h; Inert atmosphere
Precatalyst (50 mg), NaBH4 (or NaBD4) (3e12 mmol), 1 mmol ofthe N-cyclic substrate and 5 ml deionized and degassed water (orD2O) were placed in a 25 ml three-necked flask equipped with areflux condenser and a pressure release valve to discharge thehydrogen gas self-generated during the reactions. The operationwas carried out under inert atmosphere. The reaction mixture wasvigorously stirred at different temperatures (25e60 C) for the timeselected. The complete conversion of substrate was determined bysubmitting small samples to spot thin layer chromatography (TLC).After completion, the slurry was centrifuged to separate the catalyst.The solid phase obtained was washed with deionized H2O andthen several times with ethyl acetate to remove all organic residue.The filtrate was collected, extracted with ethyl acetate and theextract dried over anhydrous MgSO4. After removal of the solvent invacuo, the corresponding product was obtained. In some cases, asilica-gel column chromatography was used to purify the product(isolated yield). The product analysis and identification was conductedby comparing the NMR spectral data with those of thepublished pure substances (all analyzed by 1H NMR and 13C NMRon Bruker Avance II 400 MHz spectrometer). The reaction selectivitieswere obtained from the NMR spectra by integration ofcharacteristic peaks for the product and reactant.
91%
Stage #1: With H2SiEt2; tris(pentafluorophenyl)borate In chloroform at 85℃; for 2 h; Inert atmosphere Stage #2: With hydrogenchloride In diethyl ether at 20℃; for 1 h;
General procedure: In a 1.5 mL reaction vial, B(C6F5)3 (0.025 mmol, 5.0 mol percent) was dissolved in chloroform (0.60 mL), towhich diethylsilane (1.75 mmol, 3.5 equiv) was added. After shaking briefly, quinolines (1a-p, 0.50 mmol, 1.0equiv) was subsequently added to the above catalyst solution under argon atmosphere. The reaction mixturewas stirred at 25-65 oC for 6-24 h for the reaction of 1a-h, and at 25-100 oC for 2-24 h for the reaction of 1i-p,then allowed to cool down to room temperature and concentrated under reduced pressure to give the crudeproduct. This reaction mixture was then treated with 0.25 N HCl ethereal solution (7 mL) and stirred at roomtemperature for 1 h to give the solid residue, which was subsequently washed with ether. The solid residue wasthen dissolved or suspended in MeOH (1.0 mL) and neutralized with Na2CO3·H2O (0.5 g) at 0 oC. After stirringfor 2 h, MeOH was removed under reduced pressure, and the neutralized reaction residue was dissolved inCH2Cl2 and washed with brine (5 mL) and water (5 mL). The crude product was then obtained from the organicphase of CH2Cl2 solution and finally purified by column chromatography on silica gel to give 2a-h(EtOAc/Hexane = 1/9) and 2i-p (EtOAc/Hexane = 3/7).
Reference：
[1] Chemical Communications, 2013, vol. 49, # 63, p. 7052 - 7054
[2] Patent: CN105884684, 2016, A, . Location in patent: Paragraph 0018; 0019
[3] Journal of Organic Chemistry, 2008, vol. 73, # 21, p. 8639 - 8642
[4] Tetrahedron, 2009, vol. 65, # 47, p. 9737 - 9741
[5] Journal of Organometallic Chemistry, 2016, vol. 821, p. 197 - 205
[6] Chemistry - A European Journal, 2016, vol. 22, # 48, p. 17151 - 17155
[7] Synlett, 2017, vol. 28, # 18, p. 2396 - 2400
[8] ACS Catalysis, 2016, vol. 6, # 9, p. 5816 - 5822
[9] Advanced Synthesis and Catalysis, 2016, vol. 358, # 19, p. 3039 - 3045
[10] Advanced Synthesis and Catalysis, 2015, vol. 357, # 4, p. 753 - 760
[11] Organic Letters, 2018, vol. 20, # 14, p. 4159 - 4163
[12] Angewandte Chemie - International Edition, 2016, vol. 55, # 1, p. 292 - 296[13] Angew. Chem., 2016,
[14] Chemical Science, 2018, vol. 9, # 42, p. 8134 - 8141
[15] Synthetic Communications, 1998, vol. 28, # 3, p. 485 - 492
[16] ChemCatChem, 2013, vol. 5, # 8, p. 2183 - 2186
[17] Chemische Berichte, 1881, vol. 14, p. 1368
[18] Journal of the American Chemical Society, 1944, vol. 66, p. 1166,1168
[19] Helvetica Chimica Acta, 1949, vol. 32, p. 1278,1281
[20] Helvetica Chimica Acta, 1949, vol. 32, p. 1278,1281
[21] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 1933 - 1939
[22] Patent: US4843082, 1989, A,
[23] Synthesis, 2011, # 13, p. 2079 - 2084
[24] Journal of the American Chemical Society, 2012, vol. 134, # 42, p. 17592 - 17598,7
[25] RSC Advances, 2013, vol. 3, # 46, p. 23984 - 23988
[26] Tetrahedron Letters, 2016, vol. 57, # 3, p. 329 - 332
[27] Journal of the American Chemical Society, 2017, vol. 139, # 28, p. 9419 - 9422
[28] Chemistry - A European Journal, 2017, vol. 23, # 57, p. 14167 - 14172
[29] Molecular Catalysis, 2018, vol. 452, p. 145 - 153
[30] Catalysis Science and Technology, 2018, vol. 8, # 19, p. 5019 - 5097
22
[ 148-24-3 ]
[ 32258-81-4 ]
[ 6640-50-2 ]
Reference：
[1] Synlett, 2004, # 15, p. 2827 - 2829
23
[ 148-24-3 ]
[ 7664-93-9 ]
[ 7732-18-5 ]
[ 6640-50-2 ]
Reference：
[1] Helvetica Chimica Acta, 1949, vol. 32, p. 1278,1281
24
[ 148-24-3 ]
[ 1127-45-3 ]
Yield
Reaction Conditions
Operation in experiment
97%
With manganese dioxide; dihydrogen peroxide In dichloromethane
(1) 8-Hydroxyquinoline N-oxide 59.74 g (411 mmol) of 8-hydroxyquinoline, 350 ml (822 mmol) of dichloromethane, 82.2 ml of 35percent aqueous hydrogen peroxide solution and 0.52 g (2.5 mmol) of methylrhenium trioxide (MTO) are placed in a 1 L round-bottomed flask. The reaction mixture is stirred at room temperature (25° C.) for 24 hours, followed by successive addition of 80 ml of aqueous hydrogen peroxide solution and 0.32 g of manganese dioxide. The mixture is stirred for 1 hour 30 minutes and the phases are then separated by settling. The aqueous phase is extracted with dichloromethane (2*200 ml). The organic phases are combined, dried over sodium sulfate, filtered and concentrated under vacuum to give 64 g of 8-hydroxyquinoline N-oxide in the form of an orange-colored solid; m.p.=112° C. (Yield: 97percent)
97%
With manganese dioxide; dihydrogen peroxide In dichloromethane
(1) 8-Hydroxyquinoline N-Oxide 59.74 g (411 mmol) of 8-hydroxyquinoline, 350 ml (822 mmol) of dichloromethane, 82.2 ml of 35percent aqueous hydrogen peroxide solution and 0.52 g (2.5 mmol) of methylrhenium trioxide (MTO) are placed in a 1 l round-bottomed flask. The reaction mixture is stirred at ambient temperature (25° C.) for 24 h and then 80 ml of aqueous hydrogen peroxide solution and 0.32 g of manganese dioxide are successively added. The mixture is stirred for 1 h 30 and then separated by settling. The aqueous phase is extracted with dichloromethane (2*200 ml). The organic phases are combined, dried over sodium sulfate, filtered and concentrated under vacuum to provide 64 g of 8-hydroxyquinoline N-oxide in the form of an organe-colored solid; M.p.=112° C. (Yield: 97percent)
95%
With dihydrogen peroxide; bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate salt In ethanol at 20℃; for 0.833333 h;
General procedure: In a 25-mL flask to a solution of Hendrickson reagent (1 mmol, 0.839 g) in 3 mL of ethanol at room temperature, H2O2 (4 mmol, 0.4 mL) was added, and the mixture allowed stirring for 15 min. Then, pyridine (1 mmol, 0.16 mL) was added to the mixture, and the solution was stirred again for appropriate time (Table 2). Upon completion of the reaction, the solvent was removed under reduced pressure, and then the saturated sodium bicarbonate solution (10 mL) was added. The product was extracted with chloroform (3 × 5 mL), washed with water, and dried over anhydrous MgSO4. The filtrate was evaporated and the crude product was purified by silica gel column chromatography using ethyl acetate/n-hexane (3:7) as eluent to afford pyridine-N-oxide (0.076 g, 80percent).
89%
With dihydrogen peroxide In water for 0.416667 h; Sonication
In a 50 mL round-bottomed flask, 1.45 g of 8-hydroxyquinoline, followed by hydrogen peroxide (35percent by mass), 1.1 g, 5percent were added.Mass fraction of perfluorosulfonic acid resin, 10 ml of water as a solvent, and the resulting mixture at 30 W/20 KHz in an ultrasonic reactor25 minutes under acoustic conditions. The perfluorosulfonic acid resin catalyst in the reaction system is removed by filtration, and the reaction solvent is removed under reduced pressureThe water was finally recrystallized to obtain a 1.63 g 6-chloroquinoline nitrogen oxide compound in 89percent yield.
76%
With peracetic acid; acetic acid In dichloromethane; water at 0 - 20℃; for 5 h;
To a solution of 8-hydroxyquinoline (50.0 g, 344 mmol) in methylene chloride (325 mL) was added dropwise at 0° C. dilute peroxyacetic acid (Fluka, 39percent in aqueous acetic acid, 75.1 mL, 440 mol), wherein the yellow solution became deep red. After warming and stirring at room temperature for 5 h, a solution of sodium disulfite (14.0 g, 74 mmol) in water (20 mL) was added dropwise. Here the solution turned dark yellow to black. The organic phase was washed successively with 1M hydrochloric acid (ca. 300 mL), sat. sodium hydrogen carbonate solution (ca. 200 mL), sat. potassium carbonate solution (ca. 150 mL) and sat. sodium chloride solution (ca. 200 mL). The yellow-brown solution was treated with silica gel (silica gel 60 for column chromatography, 0.063-0.200 mm, 5 g) and dried with sodium sulfate. After stirring at room temperature for 15 min, the solid was separated off and the solvent was removed on a rotary evaporator. A yellow to light-brownish solid was obtained, which was dried under fine vacuum. [0094] Yield: 42.4 g (263 mmol, 76percent), yellow solid. [0095] HR-ESI/MS (CH3OH): m/z calculated for [C9H7NO2+H]+: 162.0550. found: 162.0553; m/z calculated for [C9H7NO2+Na]+: 184.0374. found: 184.0374. [0096] 1H-NMR (300.1 MHz, CDCl3): δ (ppm)=7.09 (dd, J=7.9, 1.1 Hz, 1H, H7), 7.24-7.29 (m, 2H, H3/H5), 7.51 (t, J=7.9 Hz, 1H, H6), 7.81 (dd, J=8.5, 0.6 Hz, 1H, H4), 8.26 (dd, J=6.1, 1.0 Hz, 1H, H2), 15.09 (s, 1H, OH). [0097] 13C{1H}-NMR (75.5 MHz, CDCl3): δ (ppm)=114.6 (C7), 116.6 (C5), 120.3 (C3), 129.4 (C4), 129.7 (C4a), 130.3 (C6), 132.1 (C8a), 134.3 (C2), 153.8 (C8). [0098] CHN analysis: calculated for C9H7NO2 (161.16 g/mol): C, 67.07; H, 4.38; N, 8.69 wt percent. found: C, 67.14; H, 4.19; N, 8.63 wt percent.
76%
With peracetic acid In dichloromethane; water at 0 - 20℃; for 5.25 h;
To a solution of 8-hydroxyquinoline (50.0 g, 344 mmol) in methylene chloride (325 mL) were diluted peroxyacetic acid (Fluka, ~ 39percent in aqueous acetic acid, 75.1 mL, 440 mol) was added dropwise at 0 ° C, the yellow solution turned deep red.After heating and stirring at room temperature for 5 h, a solution of sodium (14.0 g, 74 mmol) in water (20 mL) was added dropwise.In this case, the solution turned dark yellow to black.The organic phase was washed successively with 1 M hydrochloric acid (300 mL), sat.Sodium bicarbonate solution (200 mL), sat.Potassium carbonate solution (150 mL) and sat.Sodium chloride solution.(Ca. 200 mL).The yellow-brown solution was treated with silica gel (silica gel 60 for column chromatography, 0.063-0.200 mm, 5g) and drying with sodium sulfate.After stirring at room temperature for 15 min, the solid was separated and the solvent removed on a rotary evaporator.This gave a yellow to light tan solid which was dried under vacuum fine. Yield: 42.4 g (263 mmol, 76percent), yellow solid.
70.3%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; Cooling with ice
0.5 g 8-hydroxyquinolinewas dissolved in 4 mL dichloromethane and 0.69 g metachloroperbenzoicacid (m-CPBA) was added stepwise in anice-cooled water bath. The resulting mixture was stirred atroom temperature overnight. 7.14 mL 2 M NaOH wasadded slowly to the above solution. The organic layer wasseparated and the water phase was washed with dichloromethane.The organic fractions were combined andwashed with brine, dried with sodium sulfate, and thenfiltered. The organic solvent was removed under reducedpressure, resulting in 0.39 g title compound as yellow solid(yield, 70.3 percent) 1H NMR (300 MHz, CDCl3) d 8.25 (dd,J = 6.0, 0.8 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.50 (t,J = 8.0 Hz, 1H), 7.25–7.21 (m, 2H), 7.08 (dd, 1H).
40%
at 70℃; for 16 h;
A solution of quinolin-8-ol (4 g, 27.6 mmol) in 35percent hydrogen peroxide solution (10 ml) in acetic acid (25 mL) was stirred at 70 °C for 16 hours. After the reaction mixture was neutralized to pH 12 with ammonium hydroxide, it was extracted with ethyl acetate (50 mL x 3). The organic layers were combined, dried over sodium sulfate and concentrated to dryness to afford 5-2 (1.8 g, 40percent yield) as a brown solid. MS (ESI): m/z 238 [M+H]+.
Reference：
[1] Naunyn-Schmiedeberg's Archives of Pharmacology, 1999, vol. 359, # 3, p. 168 - 177
[2] ChemCatChem, 2015, vol. 7, # 23, p. 3903 - 3910
[3] Patent: US2003/97000, 2003, A1,
[4] Patent: US6617336, 2003, B1,
[5] Organic Letters, 2011, vol. 13, # 14, p. 3556 - 3559
[6] European Journal of Inorganic Chemistry, 2016, vol. 2016, # 35, p. 5449 - 5455
[7] Journal of the Iranian Chemical Society, 2018, vol. 15, # 8, p. 1843 - 1849
[8] Advanced Synthesis and Catalysis, 2004, vol. 346, # 2-3, p. 339 - 345
[9] Advanced Synthesis and Catalysis, 2005, vol. 347, # 15, p. 1958 - 1960
[10] Organic and Biomolecular Chemistry, 2014, vol. 12, # 19, p. 3026 - 3036
[11] RSC Advances, 2015, vol. 5, # 46, p. 36809 - 36812
[12] Patent: CN108003098, 2018, A, . Location in patent: Paragraph 0082; 0083; 0084
[13] Synthetic Communications, 2001, vol. 31, # 2, p. 167 - 172
[14] Organic Process Research and Development, 2004, vol. 8, # 4, p. 663 - 665
[15] New Journal of Chemistry, 2013, vol. 37, # 9, p. 2614 - 2618
[16] Tetrahedron Letters, 1988, vol. 29, # 12, p. 1351 - 1354
[17] Patent: US2015/203467, 2015, A1, . Location in patent: Paragraph 0093-0098
[18] Patent: KR2015/44896, 2015, A, . Location in patent: Paragraph 0124-0127
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[20] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1984, vol. 23, # 6, p. 496 - 497
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[22] Chemistry - A European Journal, 2005, vol. 11, # 23, p. 6818 - 6828
[23] Science China Chemistry, 2010, vol. 53, # 6, p. 1294 - 1301
[24] Patent: WO2013/169964, 2013, A1, . Location in patent: Paragraph 00265; 00266
[25] Journal of Chemical Sciences, 2010, vol. 122, # 6, p. 847 - 855
[26] Canadian Journal of Chemistry, 2005, vol. 83, # 5, p. 460 - 470
[27] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1981, vol. 17, # 1, p. 72 - 76[28] Khimiya Geterotsiklicheskikh Soedinenii, 1981, # 1, p. 89 - 94
[29] Zhurnal Obshchei Khimii, 1958, vol. 28, p. 2355,2358; engl. Ausg. S. 2393, 2395
[30] Nippon Kagaku Zasshi, 1954, vol. 75, p. 1180,1181[31] Chem.Abstr., 1955, p. 10785
[32] Tetrahedron, 1986, vol. 42, # 18, p. 5065 - 5071
[33] Synlett, 2006, # 6, p. 924 - 926
[34] Journal of the American Chemical Society, 2009, vol. 131, # 39, p. 13888 - 13889
[35] Journal of Molecular Catalysis A: Chemical, 2011, vol. 337, # 1-2, p. 45 - 51
[36] Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3151 - 3159
[37] Patent: US2012/46467, 2012, A1, . Location in patent: Page/Page column 19
[38] European Journal of Organic Chemistry, 2016, vol. 2016, # 8, p. 1606 - 1611
[39] Organic Letters, 2016, vol. 18, # 8, p. 1796 - 1799
[40] Green Chemistry, 2016, vol. 18, # 12, p. 3518 - 3521
[41] Organic Letters, 2016, vol. 18, # 10, p. 2495 - 2498
[42] RSC Advances, 2016, vol. 6, # 63, p. 58118 - 58124
[43] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 19, p. 4741 - 4749
[44] Chemical Communications, 2001, # 5, p. 487 - 488
[45] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5576 - 5585
[46] Advanced Synthesis and Catalysis, 2018, vol. 360, # 5, p. 905 - 910
25
[ 148-24-3 ]
[ 1127-45-3 ]
Reference：
[1] Patent: US5646164, 1997, A,
26
[ 148-24-3 ]
[ 64741-01-1 ]
[ 1127-45-3 ]
Reference：
[1] Patent: US5021567, 1991, A,
27
[ 79-21-0 ]
[ 148-24-3 ]
[ 1127-45-3 ]
Reference：
[1] Trans. Kentucky Acad., 1956, vol. 17, p. 135,137
[2] Zhurnal Obshchei Khimii, 1958, vol. 28, p. 2355,2358; engl. Ausg. S. 2393, 2395
28
[ 148-24-3 ]
[ 2311-91-3 ]
[ 1127-45-3 ]
Reference：
[1] Nippon Kagaku Zasshi, 1954, vol. 75, p. 1180,1181[2] Chem.Abstr., 1955, p. 10785
[3] Journal of the Chemical Society, 1954, p. 570,572
29
[ 148-24-3 ]
[ 93-59-4 ]
[ 1127-45-3 ]
Reference：
[1] Zhurnal Obshchei Khimii, 1958, vol. 28, p. 2355,2358; engl. Ausg. S. 2393, 2395
[2] Zhurnal Obshchei Khimii, 1952, vol. 22, p. 1224,1226; engl. Ausg. S. 1269, 1[3] Engl. Ausg. S. 1269, 1270,
30
[ 148-24-3 ]
[ 67-66-3 ]
[ 2598-30-3 ]
Yield
Reaction Conditions
Operation in experiment
115 mg
Stage #1: With sodium hydroxide In ethanol; water Stage #2: With water In ethanol for 20 h; Reflux Stage #3: With hydrogenchloride In water
8-Hydroxyquinoline (5 g, 0.3 mol) was dissolved in ethanol (50 mL) to which was added sodium hydroxide (10 g, 0.25 mol) dissolved in water (15 mL). The solution was refluxed during which time chloroform was added dropwise over 30 min. After refluxing for 20 h, ethanol and excess chloroform were evaporated in vacuo. The resulting residue was dissolved in 150 mL of water and the solution was made slightly acidic by adding dilute hydrochloric acid. The resulting yellow colored solid was extract with dichloromethane then purified by column chromatography (silica gel, dichloromethane/methanol) to afford the title product as a white solid (115 mg, 0.67 mmol). 1H-NMR (CDCl3-400 MHz) d = 10.16 (s, 1H), 9.71 (dd, 1H, J = 1.6Hz, 8.4Hz), 8.89 (dd, 1H, J = 1.6Hz, 4.0Hz), 8.02 (d, 1H, J = 8.0Hz), 7.69 (q, 1H, J = 4.0Hz), 7.30 (d, 1H, J = 8.0Hz); 13C-NMR (DMSO-d6-400 MHz) d = 193.1, 160.5, 149.9, 141.1, 138.9, 133.9, 127.7, 125.5, 123.4, 111.7.
Reference：
[1] Journal of Coordination Chemistry, 2012, vol. 65, # 9, p. 1632 - 1644
[2] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 3774 - 3781
[3] Journal of the Chilean Chemical Society, 2012, vol. 57, # 3, p. 1287 - 1291
[4] Farmaco, 1993, vol. 48, # 5, p. 615 - 636
[5] Gazzetta Chimica Italiana, 1995, vol. 125, # 2, p. 69 - 76
[6] Macromolecules, 2003, vol. 36, # 6, p. 1766 - 1768
[7] Journal of the American Chemical Society, 2008, vol. 130, # 50, p. 16959 - 16967
[8] Russian Journal of General Chemistry, 2009, vol. 79, # 5, p. 991 - 995
[9] Journal of the Chemical Society, 1955, p. 3552
[10] Nippon Kagaku Zasshi, 1956, vol. 77, p. 1107[11] Chem.Abstr., 1959, p. 5267
[12] Helvetica Chimica Acta, 1956, vol. 39, p. 1676,1680
[13] Journal of Materials Chemistry, 1998, vol. 8, # 1, p. 81 - 84
[14] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2000, vol. 56, # 7, p. 1399 - 1407
[15] Chemical Communications, 2006, # 8, p. 880 - 881
[16] Journal of Polymer Science, Part A: Polymer Chemistry, 2010, vol. 48, # 9, p. 1943 - 1951
[17] Inorganic Chemistry Communications, 2011, vol. 14, # 8, p. 1224 - 1227
[18] Tetrahedron Letters, 2011, vol. 52, # 34, p. 4385 - 4387
31
[ 148-24-3 ]
[ 2598-30-3 ]
Reference：
[1] Archiv der Pharmazie (Weinheim, Germany), 1958, vol. 291, p. 493,502
[2] Journal of the American Chemical Society, 1955, vol. 77, p. 6671,6672
[3] Journal of the American Chemical Society, 1955, vol. 77, p. 6671,6672
32
[ 148-24-3 ]
[ 67-66-3 ]
[ 2598-30-3 ]
[ 5683-78-3 ]
Reference：
[1] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical, 1989, vol. 28, # 8, p. 719 - 721
33
[ 56-23-5 ]
[ 148-24-3 ]
[ 64-17-5 ]
[ 67-66-3 ]
[ 7732-18-5 ]
[ 2598-30-3 ]
Reference：
[1] Helvetica Chimica Acta, 1956, vol. 39, p. 1676,1680
[2] Journal of the Chemical Society, 1955, p. 3552
[3] Nippon Kagaku Zasshi, 1956, vol. 77, p. 1107[4] Chem.Abstr., 1959, p. 5267
34
[ 148-24-3 ]
[ 1198-14-7 ]
Reference：
[1] Synthetic Communications, 2010, vol. 40, # 5, p. 647 - 653
[2] Oriental Journal of Chemistry, 2011, vol. 27, # 2, p. 429 - 434
35
[ 148-24-3 ]
[ 1198-14-7 ]
[ 521-74-4 ]
Reference：
[1] Chemical Science, 2018, vol. 9, # 7, p. 1782 - 1788
[2] Journal fuer Praktische Chemie (Leipzig), 1891, vol. <2> 44, p. 439,442
Reference：
[1] Chemische Berichte, 1886, vol. 19, p. 2468[2] Monatshefte fuer Chemie, 1887, vol. 8, p. 311
[3] Chemische Berichte, 1916, vol. 49, p. 16
[4] Journal of the American Chemical Society, 1935, vol. 57, p. 124,127
38
[ 148-24-3 ]
[ 6541-19-1 ]
Yield
Reaction Conditions
Operation in experiment
29%
With hydrogenchloride; sodium chlorate In water for 2 h;
Sodium chlorate (0.50 mol) was added over a period of 1 h to a solution of 8-hydroxyquinoline (0.10 mol) in concd HCl (600 mL) at 40 °C and the reaction mixture stirred for 2 h before being diluted with water to a total volume of 2 L. The white precipitate that formed was removed by filtration and discarded. The filtrate was then extracted with CH2Cl2 (6 * 250 mL), the organic phases were combined, washed with water and concentrated in vacuo to give a yellow solid. The solid was then recrystallized in MeOH to yield 7 as bright yellow crystals. The characterization data for compound 7 are in accordance with that reported previously [ 32 ].
12%
With hydrogenchloride; calcium chlorate In water
Example 1; Quinoline Phthalocyanine; a) 6,7-dicyano-5,8-dihydroxyquinoline 3; 6,7-Dichloro-5,8-quinolinedione 2 was prepared in low yield from commercially available 8-hydroxyquinoline 1 by modification of a literature procedure (Shaikh, I. A.; Johnson, F.; Grollman, A. P. J. Med. Chem. 1986, 29, 1329). A solution of potassium cyanide (1.02 g; 16 mmol) in water (3 mL) was added to a boiling solution of the dichloroquinone 2 (794 mg; 3.48 mmol) in THF/methanol (1:1, 40 mL) and heating was continued for a further 2 min. The reaction mixture was concentrated to half-volume and diluted to the original volume with water. Hydrochloric acid (10 M) was added cautiously [Caution: HCN fumes] causing the reaction mixture to change from an olive-green solution to a pale brown suspension. The solid was filtered off, washed with water and air dried overnight thereby affording the dinitrile 3 as a chocolate-brown solid (509 mg, 69percent).
Reference：
[1] RSC Advances, 2015, vol. 5, # 78, p. 63330 - 63337
[2] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 8, p. 4617 - 4625
[3] Journal of Medicinal Chemistry, 1986, vol. 29, # 8, p. 1329 - 1340
[4] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 9, p. 3238 - 3251
[5] European Journal of Medicinal Chemistry, 2018, vol. 157, p. 423 - 436
[6] Patent: US2006/30701, 2006, A1, . Location in patent: Page/Page column 25-26
[7] Chemistry of Heterocyclic Compounds, 2012, vol. 48, # 6, p. 888 - 891[8] Khim. Geterotsikl. Soedin., 2012, vol. 48, # 6, p. 955 - 959,5
[9] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1572 - 1577
39
[ 67-56-1 ]
[ 148-24-3 ]
[ 6541-19-1 ]
Reference：
[1] Chemical Communications, 2018, vol. 54, # 8, p. 992 - 995
40
[ 148-24-3 ]
[ 64-17-5 ]
[ 6541-19-1 ]
Reference：
[1] Chemical Communications, 2018, vol. 54, # 8, p. 992 - 995
41
[ 71-23-8 ]
[ 148-24-3 ]
[ 6541-19-1 ]
Reference：
[1] Chemical Communications, 2018, vol. 54, # 8, p. 992 - 995
42
[ 148-24-3 ]
[ 67-63-0 ]
[ 6541-19-1 ]
Reference：
[1] Chemical Communications, 2018, vol. 54, # 8, p. 992 - 995
43
[ 148-24-3 ]
[ 71-36-3 ]
[ 6541-19-1 ]
Reference：
[1] Chemical Communications, 2018, vol. 54, # 8, p. 992 - 995
44
[ 148-24-3 ]
[ 773-76-2 ]
[ 130-16-5 ]
Reference：
[1] Chemical Science, 2018, vol. 9, # 7, p. 1782 - 1788
[2] Journal of the Indian Chemical Society, 1945, vol. 22, p. 171
45
[ 148-24-3 ]
[ 773-76-2 ]
Reference：
[1] Chemische Berichte, 1888, vol. 21, p. 2979,2983
[2] Chemische Berichte, 1897, vol. 30, p. 2420[3] Journal fuer Praktische Chemie (Leipzig), 1897, vol. <2> 56, p. 282
[4] Chemische Berichte, 1919, vol. 52, p. 193
[5] Chemische Berichte, 1897, vol. 30, p. 2420[6] Journal fuer Praktische Chemie (Leipzig), 1897, vol. <2> 56, p. 282
[7] Chemische Berichte, 1888, vol. 21, p. 2979,2983
[8] RSC Advances, 2015, vol. 5, # 107, p. 88311 - 88315
[9] DRP/DRBP Org.Chem.,
46
[ 148-24-3 ]
[ 83-73-8 ]
Yield
Reaction Conditions
Operation in experiment
87%
at 80℃; for 1 h; Inert atmosphere
8-Hydroxyquinoline (0.1 g, 0.69 mmol) and l-butyl-3-methylpyridinium dichloroiodate (BMPDCI) (0.31 g, 0.89 mmol) were added in 10 ml of one neck round bottomed flask in an inert atmosphere and then heated at 80 °C for lhr. After the reaction was completed (TLC), ethyl acetate (10ml) was added followed by addition of water (10ml). The entire reaction mixture was extracted with ethyl acetate (3x10ml). The combined organic layers were dried using sodium sulphate and concentrated on rotavapor to afford the crude product. This was further purified by silica gel column chromatography to afford 0.24 g (87 percent) of pure 5,7- diiodo-8-hydroxyquinoline as a solid. (M.P. decomposes >210 °C) 1H NMR (DMSO-d6 δ/ppm): 8.88 (d, 1H, 7=4 Hz, Ar-H), 8.3 (s, 1H, Ar-H), 8.27-8.31 (dd, 1H, 7=1.3 Hz, 8.6 Hz, Ar-H), 7.75 (q, 1H, 7=4.2 Hz, 8.6 Hz, Ar-H).
82%
With sodium periodate; sulfuric acid; iodine; potassium iodide; sodium sulfite In water; acetic acid at 25℃; for 3 h;
General procedure: Iodination of phenol (1d) in the presence of Na2SO3 (typical procedure). A 100-mL round-bottom flask was charged with a solution of 3 mmol of phenol in 10 mL of acetic acid, and a solution of KI3 and Na2SO3 (prepared preliminarily by addition of 3 mmol of iodine and 3 mmol of Na2SO3 to a solution of 3 mmol of potassium iodide in 3 mL of water) was added rapidly. At the same time, a solution of 3 mmol of NaIO4 in 5 mL of water was added, and 0.5 mL of sulfuric acid was rapidly added using a pressure-equalizing dropping funnel. The mixture was stirred at 25°C, the progress of the reaction being monitored by TLC. When the reaction was complete, the mixture was poured into ice-cold water, and the solid product was separated by vacuum filtration, washed twice with deionized water, and dried.
Reference：
[1] Tetrahedron, 2008, vol. 64, # 1, p. 234 - 239
[2] Tetrahedron Letters, 2001, vol. 42, # 11, p. 2089 - 2092
[3] Patent: WO2016/113757, 2016, A1, . Location in patent: Page/Page column 18-19
[4] Molecules, 2005, vol. 10, # 10, p. 1307 - 1317
[5] Monatshefte fur Chemie, 2012, vol. 143, # 4, p. 619 - 623
[6] Russian Journal of Organic Chemistry, 2016, vol. 52, # 3, p. 433 - 436[7] Zh. Org. Khim., 2016, vol. 52, # 3, p. 433 - 436,4
[8] Afinidad, 1951, vol. 28, p. 163,166
[9] Chemische Berichte, 1952, vol. 85, p. 104,106
[10] Trudy Inst. c. chim. Reakt., 1939, vol. 16, p. 80,82[11] Chem.Abstr., 1940, p. 2745
[12] Journal fuer Praktische Chemie (Leipzig), 1936, vol. <2> 145, p. 257,261
[13] Journal of the American Chemical Society, 1936, vol. 58, p. 1314
[14] Bulletin de la Societe Chimique de France, 1954, p. 226
[15] Journal of Organic Chemistry, 1957, vol. 22, p. 1111
[16] Journal of Fluorescence, 2018, vol. 28, # 5, p. 1121 - 1126
47
[ 148-24-3 ]
[ 13207-63-1 ]
[ 83-73-8 ]
Reference：
[1] Journal fuer Praktische Chemie (Leipzig), 1936, vol. <2> 145, p. 257,261
[2] Journal of the Indian Chemical Society, 1944, vol. 21, p. 354,356
[3] Trans. elektroch. Soc., 1939, vol. 75, p. 385
48
[ 7647-01-0 ]
[ 148-24-3 ]
[ 7732-18-5 ]
[ 7790-99-0 ]
[ 83-73-8 ]
Reference：
[1] Journal of Organic Chemistry, 1957, vol. 22, p. 1111
49
[ 148-24-3 ]
[ 4008-48-4 ]
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[1] ACS Chemical Neuroscience, 2014, vol. 5, # 10, p. 952 - 962
[2] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1997, vol. 36, # 11, p. 1071 - 1073
[3] Chemistry of Heterocyclic Compounds, 2005, vol. 41, # 8, p. 1027 - 1030
[4] Russian Journal of Organic Chemistry, 2004, vol. 40, # 1, p. 93 - 96
[5] Journal fuer Praktische Chemie (Leipzig), 1892, vol. <2> 45, p. 540
[6] Molecules, 2010, vol. 15, # 1, p. 288 - 304
[7] Archives of Pharmacal Research, 2013, vol. 36, # 1, p. 32 - 40
[8] Dalton Transactions, 2015, vol. 44, # 48, p. 20913 - 20925
[9] RSC Advances, 2016, vol. 6, # 9, p. 7139 - 7158
[10] Asian Journal of Chemistry, 2017, vol. 29, # 4, p. 742 - 748
[11] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1572 - 1577
[12] Medicinal Chemistry Research, 2018, vol. 27, # 4, p. 1093 - 1102
[13] Journal of Fluorescence, 2018, vol. 28, # 5, p. 1121 - 1126
With sodium chloride; sulfuric acid; sodium hydrogencarbonate; potassium carbonate In chlorobenzene
EXAMPLE 1 m-Hydroxybenzyl alcohol (50.0 g; 0.40 mole), 90.0 g (0.80 mole) of chlorobenzene, 156.6 g (1.37 moles) of N,N'-dimethylimidazolidinone and 41.8 g (0.30 mole) of potassium carbonate were mixed, and 0.8 g of cuprous chloride and 1.2 g of 8-hydroxyquinoline were added. The mixture was heated to 150oC in an inert gaseous atmosphere. The mixture was stirred for 17 hours while continuing refluxing and dehydration. During this time, the reaction temperature gradually rose and reached 162oC at the end of 17 hours. The mixture was further heated to 170oC, and stirred for 3 hours at this temperature. After the reaction, the reaction mixture was cooled and 200 ml of 5percent cold dilute sulfuric acid was added. The mixture was extracted with ether, and the ethereal layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. GLC analysis showed that the conversion of m-hydroxybenzyl alcohol was 100 percent, the selectivity of m-phenoxybenzyl alcohol was 93 percent, and the yield of m-phenoxybenzyl alcohol was 93 percent.
Reference：
[1] European Journal of Organic Chemistry, 2016, vol. 2016, # 8, p. 1606 - 1611
58
[ 148-24-3 ]
[ 56826-69-8 ]
Reference：
[1] Russian Journal of Organic Chemistry, 2000, vol. 36, # 3, p. 446 - 447
59
[ 148-24-3 ]
[ 50-00-0 ]
[ 4053-45-6 ]
Yield
Reaction Conditions
Operation in experiment
98%
With hydrogenchloride In water at 0 - 20℃; for 8 h;
A mixture of 14.6 g (0.1 mol) of 8-quinolinol, 16 mL of 32percent HC1 in water, and 16 mL (0.1 mL) of 37percent formaldehyde in water at 0 °C was treated with hydrogen chloride gas for 6 h. The solution was allowed to stand at room temperature for 2 h without stirring. The yellow solid obtained was collected on a filter, washed with 90percent alcohol and dried under vacuum to give 5-chloromethyl-8-quinolinol hydrochloride A (19.0 g, 98percent): 1H NMR (250 MHz, CDC13, 5) 5.32 (s, 2H), 7.53 (m, 1H), 7.85 (m, 2H), 8.12 (m, 1H), 9.12 (m, 1H), 9.28 (m, 1H).
98%
With hydrogenchloride In water at 20℃; for 6 h;
Thus, a mixture of 10.0 g (0.068 mol) of 8-hydroxyquinoline, 11 ml of concentrated hydrochloric acid, and 11 ml (0.397 mol) of 37percent formaldehyde was treated with hydrogen chloride gas and stirred for 6 h. The solution was allowed to stand at room temperature for 2 h without stirring. The obtained yellow solid was collected on a filter, washed with acetone, and dried under vacuum to afford 5-chloromethyl-8-hydroxyquinoline hydrochloride (Cl-QH) (9.8 g, 98percent) without further purification, m.p.: 282 °C, Rf Value: 0.52 (n-hexane/acetone: 4/6). The 1HNMR, 13C NMR, IR and mass spectroscopy (ESI-MS) (Table 1)were used to characterize and confirm the obtained product structure
78%
With hydrogenchloride; zinc(II) chloride In water for 12 h;
A mixture of 5.84 g (40.0 mmol) of 8-quinolinol, 50 ml of concentrated hydrochloric acid, and 6.4 ml of 37percent formaldehyde was treated with 0.6 g of zinc chloride and stirred for 12 h. The mixture was filtered,washed with copious acetone and dried to give compound 2 as a yellow solid (7.2g, 78percent). 1H NMR (400 MHz, Deuterium Oxide) δ 9.12 (dd, J = 8.7, 1.4 Hz, 1H), 8.88 (dd, J = 5.5, 1.4 Hz, 1H), 7.97 (dd, J = 8.7, 5.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 7.9 Hz, 1H), 4.93 (s, 2H).
78%
With hydrogenchloride In water at 20℃; for 8 h; Cooling with ice
To a 100 mL round bottom flask was added 14. 50 g (100 mmol) of 8-hydroxyquinoline,16 mL concentrated hydrochloric acid,16 mL of 37percent formaldehyde solution,Hydrogen chloride gas was bubbled under ice bath for 6h,Stirring at room temperature for 2h,Filtration,Washed,Vacuum drying,To give a yellow solid15. 12 g,Yield 78percent.
77.5%
With hydrogenchloride In water at 0 - 20℃; for 10 h;
To a cooled solution of comercial 8-hydroxyquinoline (14.6 g, 100 mmol) in conc. HCl (44 mL) at 0 °C, a 37percent aqueous formaldehyde solution (20 mL) was added. Then HCl gas was bubbled through the solution with stirring for 2 h. The mixture was allowed to warm to rt with further stirring for 6 h and without stirring for 2 h more. The product was filtered and the solid was rinsed with conc. HCl, giving product 9 (19.9 g, 77.5percent) as light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 5.30 (s, 2H), 7.51 (d, J= 8.0 Hz, 1H), 7.86 (d, J= 8.0 Hz, 1H), 8.13 (dd, J= 8.7, 5.2 Hz, 1H), 9.12 (dd, J= 5.1, 1.3 Hz, 1H), 9.24 (dd, J= 8.8, 1.3 Hz, 1H).
69%
With hydrogenchloride In water at 50℃; for 8 h;
CHQ was synthesized according to the literature [28]. Briefly, a stream of HCl gas was bubbled into the solutionof 8-hydroxyquinoline (1.45 g, 10 mmol) in concentrated HCl (5 mL) and aqueous solution of formaldehyde 37percent(2 mL) under stirring at 50°C for 8 h. The reaction mixture was then filtered and the residual solid was washed with concentrated HCl (4 × 5 mL) and dried under vacuum.Compound was obtained as a yellow solid (1.3 g,69percent). FTIR (KBr): ν 2100–3100 (O―H), 2835 (CH2),1547, 1597 (C=C), 1497 (CH2)OOP, 1200–1300 (C―O),785, 725 (C―Cl) cm−1.
68%
With hydrogenchloride In water at 25℃; for 6 h;
Hydrochloric acid at 37percent (10 ml) is added, dropwise, with vigorous stirring, to a suspension of 8-hydroxyquinoline (2.9 g; 20 mmol) in formaldehyde (4 ml). The medium becomes homogeneous and bright yellow and heat is strongly given off during the addition. Hydrochloric acid gas is bubbled through the medium for 1 h and then the stirring is continued for 5 h. The temperature gradually decreases to approximately 25° C. and a fine yellow precipitate appears. The medium is then filtered and the residual yellow solid is washed with hydrochloric acid at 37percent (4×5 ml), and then dried under a high vacuum. Compound 7 is obtained in the form of a bright yellow hygroscopic solid (3.15 g; 13.7 mmol; 68percent) immediately stored under argon at 4° C. 1H NMR (DMSO-d6, 300 MHz) δ (ppm): 9.24 (dd, 4J=1.2 Hz, 3J=8.7 Hz, 1H); 9.13 (dd, 4J=1.2 Hz, 3J=5.2 Hz, 1H); 8.13 (dd, 3J=5.2 Hz, 3J=8.7 Hz, 1H); 7.87 (d, 3J=8.1 Hz, 1H); 7.54 (d, 3J=8.1 Hz, 1H); 5.32 (s, 2H). 13C NMR (DMSO-d6, 75 MHz) δ (ppm): 149.5; 144.4; 142.9; 132.3; 129.6; 127.8; 124.6; 122.8; 115.2; 43.1.
Reference：
[1] Journal of Medicinal Chemistry, 2014, vol. 57, # 24, p. 10455 - 10463
[2] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 3, p. 773 - 783
[3] Patent: WO2012/20389, 2012, A1, . Location in patent: Page/Page column 22
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 21, p. 8616 - 8637
[5] Journal of Molecular Liquids, 2016, vol. 219, p. 396 - 404
[6] Journal of Medicinal Chemistry, 2018, vol. 61, # 5, p. 1871 - 1894
[7] Chemistry - A European Journal, 2013, vol. 19, # 9, p. 3029 - 3036
[8] Green Chemistry, 2014, vol. 16, # 4, p. 2273 - 2280
[9] New Journal of Chemistry, 2010, vol. 34, # 2, p. 325 - 330
[10] Macromolecules, 2005, vol. 38, # 21, p. 8671 - 8678
[11] Molecules, 2007, vol. 12, # 5, p. 1191 - 1201
[12] Molecules, 2008, vol. 13, # 4, p. 922 - 930
[13] PLoS ONE, 2015, vol. 10, # 6,
[14] Patent: CN105294662, 2016, A, . Location in patent: Paragraph 0035-0039
[15] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2007, vol. 68, # 3, p. 646 - 650
[16] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2008, vol. 71, # 4, p. 1433 - 1437
[17] Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 2114 - 2125
[18] Oriental Journal of Chemistry, 2010, vol. 26, # 4, p. 1431 - 1436
[19] Patent: EP2727916, 2014, A1, . Location in patent: Paragraph 0092-0093
[20] Journal of Fluorescence, 2018, vol. 28, # 3, p. 767 - 774
[21] Organic and Biomolecular Chemistry, 2013, vol. 11, # 5, p. 773 - 780
[22] Patent: US2015/38493, 2015, A1, . Location in patent: Paragraph 0183-0185
[23] Journal of the Indian Chemical Society, 1997, vol. 74, # 4, p. 287 - 288
[24] Synthetic Communications, 2000, vol. 30, # 11, p. 1927 - 1935
[25] Biochemical Pharmacology, 2005, vol. 70, # 11, p. 1642 - 1652
[26] Journal of Organic Chemistry, 2010, vol. 75, # 18, p. 6275 - 6278
[27] E-Journal of Chemistry, 2010, vol. 7, # 3, p. 1023 - 1028
[28] Inorganica Chimica Acta, 2012, vol. 383, p. 132 - 136
[29] Patent: WO2013/115793, 2013, A1, . Location in patent: Page/Page column 19
[30] Applied Catalysis A: General, 2014, vol. 470, p. 104 - 114
[31] ACS Catalysis, 2014, vol. 4, # 5, p. 1419 - 1425
[32] RSC Advances, 2015, vol. 5, # 21, p. 16207 - 16222
[33] Physical Chemistry Chemical Physics, 2018, vol. 20, # 30, p. 20167 - 20187
60
[ 7647-01-0 ]
[ 148-24-3 ]
[ 50-00-0 ]
[ 7732-18-5 ]
[ 4053-45-6 ]
Reference：
[1] Archiv der Pharmazie (Weinheim, Germany), 1958, vol. 291, p. 493,502
General procedure: Cu (II) and Co (II) ions was synthesized by modifyingliterature methods8.1mmole of 8-hydroxyquinolinewas dissolved in alcoholic KOH. This solution wasadded drop wise to the solution of 1mmole metalsalt in alcohol. The reaction mixture was reuxedfor appropriate time. The solid product was obtainedafter completion of the reaction.The ligand 8-Hydroxyquinoline with Ni (II),Cu (II) and Co (II) ions was synthesized by modifyingliterature methods8.1mmole of 8-hydroxyquinolinewas dissolved in alcoholic KOH. This solution wasadded drop wise to the solution of 1mmole metalsalt in alcohol. The reaction mixture was reuxedfor appropriate time. The solid product was obtainedafter completion of the reaction.
Reference：
[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 23, p. 10448 - 10459
[2] Oriental Journal of Chemistry, 2016, vol. 32, # 6, p. 2999 - 3013
[3] Chemische Berichte, 1985, vol. 118, # 4, p. 1556 - 1563
66
[ 148-24-3 ]
[ 6046-93-1 ]
[ 10380-28-6 ]
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[1] Journal of Solid State Chemistry, 1993, vol. 106, p. 451 - 460
[2] Canadian Journal of Chemistry, 1983, vol. 61, p. 2154 - 2158
[3] Research on Chemical Intermediates, 2015, vol. 41, # 8, p. 5703 - 5712
67
[ 148-24-3 ]
[ 10380-28-6 ]
Reference：
[1] Journal of the American Chemical Society, 1957, vol. 79, p. 4041
[2] Gmelin Handbuch, Gmelin Handbook: Cu: MVol.B4, 116, page 1696 - 1699,
68
[ 148-24-3 ]
[ 10380-28-6 ]
Reference：
[1] Theoretical and Experimental Chemistry, 1989, vol. 25, p. 97 - 101[2] Teoreticheskaya i Eksperimental'naya Khimiya, 1989, vol. 25, p. 108 - 112
[3] Industrial and Engineering Chemistry, Analytical Edition, 1943, vol. 15, p. 346 - 349
[4] Analyst (Cambridge, United Kingdom), 1933, vol. 58, p. 388 - 395
[5] , 1937, vol. 26, p. 391 - 413
[6] Gmelin Handbuch, Gmelin Handbook: Cu: MVol.B4, 116, page 1696 - 1699,
[7] Gmelin Handbuch, Gmelin Handbook: Cu: MVol.B4, 116, page 1696 - 1699,
69
[ 148-24-3 ]
[ 142-71-2 ]
[ 10380-28-6 ]
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[1] Kinetics and Catalysis, 1985, vol. 26, p. 50 - 57[2] Kinetika i Kataliz, 1985, vol. 26, p. 61 - 68
[3] Gazzetta Chimica Italiana, 1923, vol. 53, p. 605 - 616
[4] Monatshefte fuer Chemie, [5] Monatshefte fuer Chemie, 1882, vol. 3, p. 531 - 569
[6] Gmelin Handbuch, Gmelin Handbook: Cu: MVol.B4, 116, page 1696 - 1699,
[7] Indian Journal of Chemistry, Section A: Inorganic, Bio-inorganic, Physical, Theoretical & Analytical Chemistry, 1990, vol. 29, # 5, p. 454 - 457
70
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[ 10380-28-6 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1761 - 1766
[2] Zeitschrift fuer Naturforschung, Teil B: Chemical Sciences, [3] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1995, vol. 50, p. 524 - 528
[4] Zeitschrift fuer Naturforschung, Teil B: Chemical Sciences, [5] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1995, vol. 50, p. 524 - 528
71
[ 148-24-3 ]
[ 10380-28-6 ]
Reference：
[1] Zeitschrift fuer Naturforschung, Teil B: Chemical Sciences, [2] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1995, vol. 50, p. 524 - 528
[3] Spectrochimica Acta, 1956, vol. 8, p. 1 - 8
[4] Zeitschrift fuer Naturforschung, Teil B: Chemical Sciences, [5] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1995, vol. 50, p. 524 - 528
[6] Gmelin Handbuch, Gmelin Handbook: Cu: MVol.B4, 116, page 1696 - 1699,
72
[ 148-24-3 ]
[ 10380-28-6 ]
Reference：
[1] Zeitschrift fuer Naturforschung, Teil B: Chemical Sciences, [2] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1995, vol. 50, p. 524 - 528
[3] Spectrochimica Acta, 1956, vol. 8, p. 1 - 8
[4] Zeitschrift fuer Naturforschung, Teil B: Chemical Sciences, [5] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1995, vol. 50, p. 524 - 528
[6] Gmelin Handbuch, Gmelin Handbook: Cu: MVol.B4, 116, page 1696 - 1699,
8-Hydroxyquinoline (5 g, 0.3 mol) was dissolved in ethanol (50 mL) to which was added sodium hydroxide (10 g, 0.25 mol) dissolved in water (15 mL). The solution was refluxed during which time chloroform was added dropwise over 30 min. After refluxing for 20 h, ethanol and excess chloroform were evaporated in vacuo. The resulting residue was dissolved in 150 mL of water and the solution was made slightly acidic by adding dilute hydrochloric acid. The resulting yellow colored solid was extract with dichloromethane then purified by column chromatography (silica gel, dichloromethane/methanol) to afford the title product as a white solid (115 mg, 0.67 mmol). 1H-NMR (CDCl3-400 MHz) d = 10.16 (s, 1H), 9.71 (dd, 1H, J = 1.6Hz, 8.4Hz), 8.89 (dd, 1H, J = 1.6Hz, 4.0Hz), 8.02 (d, 1H, J = 8.0Hz), 7.69 (q, 1H, J = 4.0Hz), 7.30 (d, 1H, J = 8.0Hz); 13C-NMR (DMSO-d6-400 MHz) d = 193.1, 160.5, 149.9, 141.1, 138.9, 133.9, 127.7, 125.5, 123.4, 111.7.
8-Hydroxyquinoline (4.6 g; 31.7 mmol) and anhydrous potassiumcarbonate (10.1 g; 73.1 mmol) in DMF (60 mL) were stirred under N2 at 90 °C for 1 h afterwhich time dimethyl sulfate (TOXIC 3 mL; 31.7 mmol) was added and the mixture was stirredfor a further 2 h at 90 oC. The cooled mixture was then diluted with water (300 mL) andextracted using dichloromethane. The combined organic layers were washed with aqueouspotassium hydroxide solution (5percent; 100 mL) in portions, and then with water until the washingswere no longer alkaline. The extract was dried, filtered and evaporated to give 8-methoxyquinoline 24 (2.67 g; 53percent), obtained as an oily solid (lit.33 mp 46-47 oC) of sufficientpurity for further use, numax (L) 3391, 3051, 3005, 2955, 2903, 2837, 1616, 1597, 1572, 1501,1472, 1440, 1424, 1378, 1317, 1263, 1224, 1194, 1174, 1111, 1077, 1031, 994, 823, 792, 753and 711 cm-1; deltaH 4.07 (3H, s, OCH3), 7.04 (1H, d, J 8 and H-7), 7.35-7.5 (3H, m, H-3, H-5 andH-6), 8.11 (1H, dd, J 8 and 1.5, H-4) and 8.91 (1H, dd, J 4.2 and 1.8, H-2) ppm.
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;
DMF (2mL) and dimethylsulfate (0.6 mmol) were added to a mixture of 8-hydroxyquinoline (0.3 mmol) and potassium carbonate (0.7mmol). The resulting suspension was allowed to stir at room temperature overnight in a sealed vessel. The mixture was then poured over water (10 mL) and the aqueous mixture as extracted with diethylether (2× 10mL). The combined organic extract was rinsed with brine (30 mL) and dried over Na2SO4. The solvent was removed under reduced pressure to afford the title compound as an off-white solid. The sample was used without further purification.
General procedure: The K2CO3 (2.7 g, 0.02 mol) or KOH (1.6 g, 0.03 mol) was addedto a solution of 5-substituted 8-hydroxy quinoline 4a?c (0.01 mol)in acetone or THF (200 mL) at ambient temperature and the mixturewas stirred for 30 min. Then the methyl iodide (CH3I) (2.8 g,0.02 mol) was added dropwise and stirred overnight. The mixturesolution was concentrated to dryness, added water and extractedwith CH2Cl2 (150 mL 3). Finally, the organic layers were combined,washed with brine, dried with Na2SO4, filtered and evaporated.5a?c were obtained as brown oil, which could be usedwithout further purification.
84%
With potassium hydroxide; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃; for 12h;
EXAMPLE 19; Preparation of Methyl [(25)-l -{(2S)-2-[5-(5-{2-[(25)-l -{(25)-2-[(methoxycarbonyl)amino]-3- methyl butanoyl }pyrrolidin-2-yl]- 1 H-imidazol-5-yl } -2,3-dihydro- 1 H-pyrido[3,2, 1 -.pound./]phenoxazin -9-yi)-l H-imidazol-2-yl]pyrrolidin- l -yl}-3-methyl- l -oxobutan-2-yl]carbamate (Compound 11); 11 - Synthesis of Compound Int-19a; A solution of 8-hydroxyquinoline (25 g, 0.172 mol), .OH (38.5 g, 0.69 mol) and Mel (16.1 mL, 0.26 mol) in THF / DMF (300 mL / 50 mL) was allowed to stir for 12 hours at room temperature. 100 mL of water was added and the mixture was concentrated in vacuo to remove THF. The resulting aqueous solution was extracted with EtOAc, and the organic extract was washed with brine, dried over Na2S0 , filtered and concentrated in vacuo. The residue obtained was purified using flash chromatography on silica gel (petroleum ether : EtOAc = 5: 1) to provide compound Int-19a as yellow oil (23 g, 84percent). NMR; (CDC13) delta 8.87 (s, 1 H), 8.07 (d, J = 7.2 Hz, 1 H), 7.33-7.41 (m, 3H), 7.00 (d, ./ = 6.0 Hz, 1 H), 4.04 (s, 3H).
84%
With potassium hydroxide; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃; for 12h;
Synthesis of Compound Int-19aInt 19aA solution of 8-hydroxyquinoline (25 g, 0.172 mol), KOH (38.5 g, 0.69 mol) andMel (16.1 mL, 0.26 mol) in THF / DMF (300 mL / 50 mL) was allowed to stir for 12 hours at room temperature. 100 mL of water was added and the mixture was concentrated in vacuo to remove THF. The resulting aqueous solution was extracted with EtOAc, and the organic extract was washed with brine, dried over Na2S04, filtered and concentrated in vacuo. The residue obtained was purified using flash chromatography on silica gel (petroleum ether : EtOAc = 5: 1) to provide compound Int-19a as yellow oil (23 g, 84percent). 1H MR: (CDC13) delta 8.87 (s, 1H), 8.07 (d, J= 7.2 Hz, 1H), 7.33-7.41 (m, 3H), 7.00 (d, J= 6.0 Hz, 1H), 4.04 (s, 3H).
8-Methoxyquinoline To a solution of 8-hydroxy quinoline (4.00 g) in DMF (60 mL) was added sodium hydride (60percent content, 1.21 g) at 0°C, followed by stirring at room temperature for 1 hour. To the reaction liquid was added methyl iodide (2.57 mL), followed by stirring for 18 hours, and the solvent was the evaporated under reduced pressure. To the residue was added water, followed by extraction with ethyl acetate, the extracted layer was dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:3) to obtain the desired product (3.50 g) as a colorless powder. EIMS (+): 159 [M]+. 1H NMR (CDCl3, 400 MHz): delta 4.10 (3H, s), 7.06 (1H, dd, J=7.9, 1.2 Hz), (7.39-7.49 (3H, m), 8.14 (1H, dd, J=8.6, 1.8 Hz), 8.93 (1H, dd, J=4.3, 1.8 Hz).
With potassium hydroxide; In tetrahydrofuran;
Add potassium hydroxide (435 g, 7.76 mol) to a solution of 8-hydroxy quinoline (250 g, 1.724 mol) in THF (10 L) at ambient temperature and stir. Add methyl iodide (435 g, 2.58 mol) dropwise and stir overnight. Filter the reaction mixture and wash the solid with THF (2 L). Concentrate the solution to dryness; add water; extract with dichloromethane (2 x 3 L); combine the organic layers; and wash with brine. Collect the organic layers and dry over sodium sulfate. Remove the solids by filtration. Collect the filtrate and concentrate under reduced pressure to give a red oil, which solidifies on standing, to give the title compound (281 g, 102percent), which can be used without further purification. ESI (m/z) 160(M+H).
With hydrogen; In water; at 20℃; under 760.051 Torr; for 0.666667h;
The 100mmol 8-hydroxy quinoline and load 0.7mmol catalyst polymer microspheres [...] Poly (DVB-co-NVP) Rh and 500 ml of water are added in a reaction kettle, to hydrogen replaces the cauldron five times the air in, and then filled with hydrogen, the reaction at normal temperature and pressure 40 minutes, the aqueous phase is extracted three times with ethyl ether, the merger ether level, ethyl ether evaporate after drying, to obtain 8-hydroxy -1, 2, 3, 4-tetrahydro-quinoline, yield 95%.
93%
With sodium tetrahydroborate; In ethanol; water; at 60℃; under 6840.46 Torr; for 3h;Inert atmosphere;Catalytic behavior;
Precatalyst (50 mg), NaBH4 (or NaBD4) (3e12 mmol), 1 mmol ofthe N-cyclic substrate and 5 ml deionized and degassed water (orD2O) were placed in a 25 ml three-necked flask equipped with areflux condenser and a pressure release valve to discharge thehydrogen gas self-generated during the reactions. The operationwas carried out under inert atmosphere. The reaction mixture wasvigorously stirred at different temperatures (25e60 C) for the timeselected. The complete conversion of substrate was determined bysubmitting small samples to spot thin layer chromatography (TLC).After completion, the slurry was centrifuged to separate the catalyst.The solid phase obtained was washed with deionized H2O andthen several times with ethyl acetate to remove all organic residue.The filtrate was collected, extracted with ethyl acetate and theextract dried over anhydrous MgSO4. After removal of the solvent invacuo, the corresponding product was obtained. In some cases, asilica-gel column chromatography was used to purify the product(isolated yield). The product analysis and identification was conductedby comparing the NMR spectral data with those of thepublished pure substances (all analyzed by 1H NMR and 13C NMRon Bruker Avance II 400 MHz spectrometer). The reaction selectivitieswere obtained from the NMR spectra by integration ofcharacteristic peaks for the product and reactant.
91%
General procedure: In a 1.5 mL reaction vial, B(C6F5)3 (0.025 mmol, 5.0 mol %) was dissolved in chloroform (0.60 mL), towhich diethylsilane (1.75 mmol, 3.5 equiv) was added. After shaking briefly, quinolines (1a-p, 0.50 mmol, 1.0equiv) was subsequently added to the above catalyst solution under argon atmosphere. The reaction mixturewas stirred at 25-65 oC for 6-24 h for the reaction of 1a-h, and at 25-100 oC for 2-24 h for the reaction of 1i-p,then allowed to cool down to room temperature and concentrated under reduced pressure to give the crudeproduct. This reaction mixture was then treated with 0.25 N HCl ethereal solution (7 mL) and stirred at roomtemperature for 1 h to give the solid residue, which was subsequently washed with ether. The solid residue wasthen dissolved or suspended in MeOH (1.0 mL) and neutralized with Na2CO3·H2O (0.5 g) at 0 oC. After stirringfor 2 h, MeOH was removed under reduced pressure, and the neutralized reaction residue was dissolved inCH2Cl2 and washed with brine (5 mL) and water (5 mL). The crude product was then obtained from the organicphase of CH2Cl2 solution and finally purified by column chromatography on silica gel to give 2a-h(EtOAc/Hexane = 1/9) and 2i-p (EtOAc/Hexane = 3/7).
In methanol; hexane; dichloromethane; hydrogen;
(A) 1,2,3,4-Tetrahydro-8-quinolinol A solution of 2.5 g (17.2 mmol) of 8-hydroxyquinoline in 50 ml of methanol was treated with 680 mg of platinum oxide and was hydrogenated in a Parr apparatus at 40 PSI until hydrogen absorption ceased. The suspension was filtered through Celite, the filtrate was evaporated and the residue was recrystallized from dichloromethane: hexane to provide 1.82 g of analytically pure, green tinged needles: melting point 117.5-119 C. A portion of this material was recrystallized once more from dichloromethane:hexane to provide a near-white solid: melting point 118-119.5 C.
With hydrogen; In methanol; at 80℃; under 750.075 Torr; for 8h;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 manganese dioxide; dihydrogen peroxide;methyl rhenium trioxide; In dichloromethane;
(1) 8-Hydroxyquinoline N-oxide 59.74 g (411 mmol) of 8-hydroxyquinoline, 350 ml (822 mmol) of dichloromethane, 82.2 ml of 35% aqueous hydrogen peroxide solution and 0.52 g (2.5 mmol) of methylrhenium trioxide (MTO) are placed in a 1 L round-bottomed flask. The reaction mixture is stirred at room temperature (25 C.) for 24 hours, followed by successive addition of 80 ml of aqueous hydrogen peroxide solution and 0.32 g of manganese dioxide. The mixture is stirred for 1 hour 30 minutes and the phases are then separated by settling. The aqueous phase is extracted with dichloromethane (2*200 ml). The organic phases are combined, dried over sodium sulfate, filtered and concentrated under vacuum to give 64 g of 8-hydroxyquinoline N-oxide in the form of an orange-colored solid; m.p.=112 C. (Yield: 97%)
97%
With manganese dioxide; dihydrogen peroxide;methyl rhenium trioxide; In dichloromethane;
(1) 8-Hydroxyquinoline N-Oxide 59.74 g (411 mmol) of 8-hydroxyquinoline, 350 ml (822 mmol) of dichloromethane, 82.2 ml of 35% aqueous hydrogen peroxide solution and 0.52 g (2.5 mmol) of methylrhenium trioxide (MTO) are placed in a 1 l round-bottomed flask. The reaction mixture is stirred at ambient temperature (25 C.) for 24 h and then 80 ml of aqueous hydrogen peroxide solution and 0.32 g of manganese dioxide are successively added. The mixture is stirred for 1 h 30 and then separated by settling. The aqueous phase is extracted with dichloromethane (2*200 ml). The organic phases are combined, dried over sodium sulfate, filtered and concentrated under vacuum to provide 64 g of 8-hydroxyquinoline N-oxide in the form of an organe-colored solid; M.p.=112 C. (Yield: 97%)
95%
With dihydrogen peroxide; bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate salt; In ethanol; at 20℃; for 0.833333h;
General procedure: In a 25-mL flask to a solution of Hendrickson reagent (1 mmol, 0.839 g) in 3 mL of ethanol at room temperature, H2O2 (4 mmol, 0.4 mL) was added, and the mixture allowed stirring for 15 min. Then, pyridine (1 mmol, 0.16 mL) was added to the mixture, and the solution was stirred again for appropriate time (Table 2). Upon completion of the reaction, the solvent was removed under reduced pressure, and then the saturated sodium bicarbonate solution (10 mL) was added. The product was extracted with chloroform (3 × 5 mL), washed with water, and dried over anhydrous MgSO4. The filtrate was evaporated and the crude product was purified by silica gel column chromatography using ethyl acetate/n-hexane (3:7) as eluent to afford pyridine-N-oxide (0.076 g, 80%).
89%
With dihydrogen peroxide; In water; for 0.416667h;Sonication;
In a 50 mL round-bottomed flask, 1.45 g of 8-hydroxyquinoline, followed by hydrogen peroxide (35% by mass), 1.1 g, 5% were added.Mass fraction of perfluorosulfonic acid resin, 10 ml of water as a solvent, and the resulting mixture at 30 W/20 KHz in an ultrasonic reactor25 minutes under acoustic conditions. The perfluorosulfonic acid resin catalyst in the reaction system is removed by filtration, and the reaction solvent is removed under reduced pressureThe water was finally recrystallized to obtain a 1.63 g 6-chloroquinoline nitrogen oxide compound in 89% yield.
85.9%
With phosphomolybdic acid; dihydrogen peroxide; In acetonitrile; at 500℃; for 30h;
As shown in Figure 1,Add 1 L of acetonitrile to the reaction flask.Add 100g of 8-hydroxyquinoline and add 350g of hydrogen peroxide.30 grams of phosphomolybdic acid,The reaction was stirred for 30 hours warming 500C;After the reaction is completed, it is cooled, and neutralized with sodium hydrogen sulfite solution until the starch-potassium iodide test paper does not change color.Evaporate acetonitrile to an internal temperature of 100 degrees, cool, stir well, filter, and dry.Obtained 94.4 g of an orange solid with a yield of 85.9%.
76%
With peracetic acid; acetic acid; In dichloromethane; water; at 0 - 20℃; for 5h;
To a solution of 8-hydroxyquinoline (50.0 g, 344 mmol) in methylene chloride (325 mL) was added dropwise at 0 C. dilute peroxyacetic acid (Fluka, 39% in aqueous acetic acid, 75.1 mL, 440 mol), wherein the yellow solution became deep red. After warming and stirring at room temperature for 5 h, a solution of sodium disulfite (14.0 g, 74 mmol) in water (20 mL) was added dropwise. Here the solution turned dark yellow to black. The organic phase was washed successively with 1M hydrochloric acid (ca. 300 mL), sat. sodium hydrogen carbonate solution (ca. 200 mL), sat. potassium carbonate solution (ca. 150 mL) and sat. sodium chloride solution (ca. 200 mL). The yellow-brown solution was treated with silica gel (silica gel 60 for column chromatography, 0.063-0.200 mm, 5 g) and dried with sodium sulfate. After stirring at room temperature for 15 min, the solid was separated off and the solvent was removed on a rotary evaporator. A yellow to light-brownish solid was obtained, which was dried under fine vacuum. [0094] Yield: 42.4 g (263 mmol, 76%), yellow solid. [0095] HR-ESI/MS (CH3OH): m/z calculated for [C9H7NO2+H]+: 162.0550. found: 162.0553; m/z calculated for [C9H7NO2+Na]+: 184.0374. found: 184.0374. [0096] 1H-NMR (300.1 MHz, CDCl3): delta (ppm)=7.09 (dd, J=7.9, 1.1 Hz, 1H, H7), 7.24-7.29 (m, 2H, H3/H5), 7.51 (t, J=7.9 Hz, 1H, H6), 7.81 (dd, J=8.5, 0.6 Hz, 1H, H4), 8.26 (dd, J=6.1, 1.0 Hz, 1H, H2), 15.09 (s, 1H, OH). [0097] 13C{1H}-NMR (75.5 MHz, CDCl3): delta (ppm)=114.6 (C7), 116.6 (C5), 120.3 (C3), 129.4 (C4), 129.7 (C4a), 130.3 (C6), 132.1 (C8a), 134.3 (C2), 153.8 (C8). [0098] CHN analysis: calculated for C9H7NO2 (161.16 g/mol): C, 67.07; H, 4.38; N, 8.69 wt %. found: C, 67.14; H, 4.19; N, 8.63 wt %.
76%
With peracetic acid; In dichloromethane; water; at 0 - 20℃; for 5.25h;
To a solution of 8-hydroxyquinoline (50.0 g, 344 mmol) in methylene chloride (325 mL) were diluted peroxyacetic acid (Fluka, ~ 39% in aqueous acetic acid, 75.1 mL, 440 mol) was added dropwise at 0 C, the yellow solution turned deep red.After heating and stirring at room temperature for 5 h, a solution of sodium (14.0 g, 74 mmol) in water (20 mL) was added dropwise.In this case, the solution turned dark yellow to black.The organic phase was washed successively with 1 M hydrochloric acid (300 mL), sat.Sodium bicarbonate solution (200 mL), sat.Potassium carbonate solution (150 mL) and sat.Sodium chloride solution.(Ca. 200 mL).The yellow-brown solution was treated with silica gel (silica gel 60 for column chromatography, 0.063-0.200 mm, 5g) and drying with sodium sulfate.After stirring at room temperature for 15 min, the solid was separated and the solvent removed on a rotary evaporator.This gave a yellow to light tan solid which was dried under vacuum fine. Yield: 42.4 g (263 mmol, 76%), yellow solid.
70.3%
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20℃;Cooling with ice;
0.5 g 8-hydroxyquinolinewas dissolved in 4 mL dichloromethane and 0.69 g metachloroperbenzoicacid (m-CPBA) was added stepwise in anice-cooled water bath. The resulting mixture was stirred atroom temperature overnight. 7.14 mL 2 M NaOH wasadded slowly to the above solution. The organic layer wasseparated and the water phase was washed with dichloromethane.The organic fractions were combined andwashed with brine, dried with sodium sulfate, and thenfiltered. The organic solvent was removed under reducedpressure, resulting in 0.39 g title compound as yellow solid(yield, 70.3 %) 1H NMR (300 MHz, CDCl3) d 8.25 (dd,J = 6.0, 0.8 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.50 (t,J = 8.0 Hz, 1H), 7.25-7.21 (m, 2H), 7.08 (dd, 1H).
40%
With dihydrogen peroxide; acetic acid; at 70℃; for 16h;
A solution of quinolin-8-ol (4 g, 27.6 mmol) in 35% hydrogen peroxide solution (10 ml) in acetic acid (25 mL) was stirred at 70 C for 16 hours. After the reaction mixture was neutralized to pH 12 with ammonium hydroxide, it was extracted with ethyl acetate (50 mL x 3). The organic layers were combined, dried over sodium sulfate and concentrated to dryness to afford 5-2 (1.8 g, 40% yield) as a brown solid. MS (ESI): m/z 238 [M+H]+.
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20℃; for 2h;Cooling with ice;
8-Quinolinol (351 g, 2.42 mol) was dissolved in dichloromethane (3.5 L) and, under ice-water cooling, meta-chloroperbenzoic acid (675.3 g, 2.74 mol) was added thereto in portions, and the mixture was stirred at room temperature for 2 hours. Insoluble matter was removed by filtration and was washed with dichloromethane. The filtrate and the washing were mixed and concentrated under reduced pressure. To the residue, 2% aqueous ammonia (2.1 L) was added and the mixture was stirred at room temperature overnight. The precipitate was collected by filtration, washed with purified water, and dried under reduced pressure to obtain 8-hydroxyquinoline-N-oxide (318.4 g). 1H-NMR(400 MHz, DMSO-d6) delta8.51(d, J=8.0 Hz, 1H), 8.06(d, J=8.0 Hz, 1H), 7.43-7.56 (m, 2H), 7.39(d, J=8.0 Hz, 1H), 6.98(d, J=8.0 Hz, 1H)
With N-Bromosuccinimide; In chloroform; at 0 - 40℃; for 18h;
To a stirred solution of quinolin-8-ol (1) (5 g, 1 mmol) in chloroform (10 mL), N-bromo succinimide (6.13 g, 1 mmol) was added portion wise at 0 C, slowly raising the temperature to 40 C and stirred for 18 h. The progress of the reaction was monitored by TLC using ethyl acetate and hexane as an eluent (1:9). After completion of the reaction, the reaction mixture was evaporated under vacuum and washed with water to give the crude 7-bromoquinolin-8-ol (2) (6.53 g), which was then washed with hexane and diethyl ether to yield 7-bromoquinolin-8-ol as a white solid in 85% yield. m.p: 138-143 C; EI-MS: m/z (%): 224 (M+ H (100)), 145 (32).
Step 1. 7-Bromoquinolin-8-ol (1a) To a flame dried 100 mL 3 neck round bottom flask containing a stirring bar and fitted with a nitrogen inlet, addition funnel and a septum was added t-butylamine (7.24 mL, 68.89 mmol) in 50 mL toluene and the reaction was cooled to -78 C. To this was slowly added bromine (1.69 mL, 32.72 mmol) via syringe. The mixture was allowed to stir for 10 min, followed by the dropwise addition of 8-hydroxyquinoline (5 g, 34.45 mmol) in 10 mL chloroform via the addition funnel. The mixture was allowed to stir for 1 hr, then warmed to ambient temperature. The mixture was then diluted to 200 mL with ethyl acetate and extracted with saturated aqueous NaHCO2, water, and brine. The organic extracts were dried over Na2SO4, filtered and the solvent removed to give the crude title material which was used in the next step without further purification. ES MS M+1=224
With ammonium hydroxide; CuI; potassium carbonate; In dimethyl sulfoxide; ethyl acetate;
Example 52 1-(4-Methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid (61). A solution of 1-(4-methoxy-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (50, 2.0 g, 6.4 mmol), 1-(4-iodo-phenyl)-piperidin-2-one (60, 2.5 g, 8.3 mmol, 1.3 equiv), and K2CO3 (325 mesh powder, 1.80 g, 12.8 mmol, 2.0 equiv) in DMSO (35 mL) was degassed three times under a steady nitrogen stream before being treated with CuI (244 mg, 1.3 mmol, 20% equiv) and 8-hydroxyquinoline (189 mg, 1.3 mmol, 20% equiv) under N2. The resulting reaction mixture was subsequently degassed three times again before being warmed up to 125 C. for 10 h. When HPLC showed the coupling reaction was complete, the reaction mixture was cooled down to 5-10 C. before being treated with 14% NH4OH aqueous solution (30 mL) and ethyl acetate (30 mL) at 5-10 C. with good stirring. The mixture was stirred for an additional 1 h at 5-10 C. The mixture was filtered through a Celite bed and the Celite bed was washed with water (2*10 mL). The two layers of the filtrates were separated, and the aqueous layer was acidified by 1 N aqueous HCl solution to pH=4. The mixture was subsequently stirred at 5-10 C. for an additional 1 h. The solids were collected by filtration, washed with water (2*5 mL), and dried in vacuo at 40-45 C. for 12 h to afford the crude desired 1-(4-methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid (61, 2.0 g, 2.95 g theoretical, 68%), which was found to be pure enough to do the following reaction without further purification. For 61, CIMS m/z 461 (M++H, C25H24N4O5).
With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; NaH; In 1,4-dioxane;
Preparation of 8-aminoquinoline To a solution of 8-hydroxyquinoline (537 mg, 3.70 mmol) in dioxane (20 mL) was added NaH (Aldrich, dry, 300 mg, 12.2 mmol) and Cs2 CO3 (4.00 g, 12.2 mmol). The resulting mixture was stirred at room temperature for about 30 minutes, then 2-bromo-2-methyl-propanamide (2.03 g, 12.2 mmol) was added and the resulting mixture was stirred at reflux for 16 h. After the reflux period, NMP (20 mL), DMPU (2 mL), and NaH (Aldrich, dry, 100 mg, 4.07 mmol) were added. The resulting mixture was stirred at 150 C. for 72 h. The reaction was cooled to room temp., and partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics washed with water (2*50 mL), dried (Na2 SO4), and concentrated to about 3 g of material. The brown oil was chromatographed on silica (200 mL, 4 cm diam. column), eluding with 30:70:1 EtOAc/hexane/NEt3 to obtain 8-aminoquinoline as an off-white solid (220 mg, 1.53 mmol, 41.3% yield).: mp 65-67 C. (lit. 62.5-64 C., Dewar, M. J. S. et. al., Journal of the Chemical Society, 1956, 2556 and 62.5-64 C., Richardson, A. et. al., Journal of Organic Chemistry, 1960, 25, 1138); 1 H NMR (300 MHz, CDCl3) delta8.76 (dd, 1 H, J=4.23, 1.75 Hz), 8.06 (dd, 1 H, J=8.20, 1.96), 7.37-7.30 (om's, 2 H), 7.15 (dd, 1 H, J=8.01, 1.30), 6.92 (dd, 1 H, J=7.51, 1.42), 4.98 (br s, 2 H, N--H2); MS (EI) 144; Analysis: Calculated C 74.98, H 5.59, N 19.43; Found C 74.88, H 5.67, N 19.26.
8-[(2,3,4,5-Tetrahydro-2-methyl-4-methylene-5-oxo-2-furanyl)methoxy]-2(1H)-quinolinone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dichloromethane;
EXAMPLE 5 8-[(2,3,4,5-Tetrahydro-2-methyl-4-methylene-5-oxo-2-furanyl)methoxy]-2(1H)-quinolinone (5) To a solution of 8-hydroxyquinoline (1.45 g, 10 mmol) in dichloromethane (50 ml) was added 3-chloroperbenzoic acid (MCPBA) (1.24 g, 13 mmol). The mixture was stirred at room temperature for 10 min, poured into 1.0N sodium bicarbonate (100 ml), and then extracted with dichloromethane (3*50 ml). The extract was washed with water, dried over magnesium sulfate, and evaporated to give a brown solid which was crystallized from dichloromethane and diethyl ether affording 8-Hydroxyquinoline 1-oxide (5a) (1.34 g, 83percent) as yellow needle crystals. mp: 132°-133° C.; 1 H-NMR (CDCl3): delta7.04-8.28 (m, 6H, Ar--H), 15.02 (br s, 1H, OH).
EXAMPLE 1 8-Hydroxyquinoline-N-Oxide In this example, 8-hydroxyquinoline-N-oxide was produced from 8-hydroxyquinoline. A stirred solution of 8-hydroxyquinoline (25.00 g, 172.2 mmol) in 550 ml of CHCl3 was cooled to 0 C., and 3 -chloroperoxybenzoic acid (40.00 g, 80% Tech. grade *0.231 mmol=0.185 mmol) was added slowly over 3 minutes. The solution was kept at 0 C. and stirred for 3 hours. During this period, the 3-chlorobenzoic acid byproduct precipitated. The 3-chlorobenzoic acid was removed by filtration and the orange filtrate was concentrated to dryness and the remaining solid was triturated with 2% NH40 H (2*200 ml). The solid was isolated on a frit and washed with H2 O.
2-[4-hydroxyphenyl]-2-[5-(8-hydroxyquinolyl)]-propane[ No CAS ]
[ 59-31-4 ]
Yield
Reaction Conditions
Operation in experiment
In dichloromethane; water;
PREPARATION OF THE STARTING MATERIAL, 2-[4-HYDROXYPHENYL]-2-[5-(8-HYDROXYQUINOLYL)]-PROPANE. 1,508 g of 8-hydroxyquinoline, 483 g of p-isopropenylphenol and 150 g of bentonite (acid catalyst K 20 from Messrs. Sudchemie, Munich) are brought together and heated to 180 C for 24 hours in a nitrogen atmosphere under reflux. The reaction miture is then filtered through a pressure filter to separate off the solid catalyst. After addition of methylene chloride/water, a part of the 2-[4-hydroxyphenyl]-2-[5-(8-hydroxyquinolyl)]-propane is obtained in a crystalline form. The mixture which remains is subjected to a steam distillation, whereby the 8-hydroxyquinoline employed in excess can be recovered. on renewed addition of methylene chloride, a further part of the functional hydroxyquinoline is obtained in a crystalline form. The two crystalline fractions, when combined, give a total yield of 460 g (46% of theory). After extraction with benzene in a Soxhlet, colourless crystals of melting point 139 C are obtained from benzene.
With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; NaH; caesium carbonate; In 1,4-dioxane;
Preparation of 8-aminoquinoline. To a solution of 8-hydroxyquinoline (537 mg, 3.70 mmol) in dioxane (20 mL) was added NaH (Aldrich, dry, 300 mg, 12.2 mmol) and Cs2CO3 (4.00 g, 12.2 mmol). The resulting mixture was stirred at room temperature for about 30 minutes, then 2-bromo-2-methyl-propanamide (2.03 g, 12.2 mmol) was added and the resulting mixture was stirred at reflux for 16 h. After the reflux period, NMP (20 mL), DMPU (2 mL), and NaH (Aldrich, dry, 100 mg, 4.07 mmol) were added. The resulting mixture was stirred at 150 C for 72 h. The reaction was cooled to room temp., and partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics washed with water (2 x 50 mL), dried (Na2SO4), and concentrated to about 3 g of material. The brown oil was chromatographed on silica (200 mL, 4 cm diam. column), eluding with 30:70:1 EtOAc/hexane/NEt3 to obtain 8-aminoquinoline as an off-white solid (220 mg, 1.53 mmol, 41.3% yield).: mp 65-67C (lit. 62.5-64 C, Dewar, M.J.S. et. al., Journal of the Chemical Society, 1956, 2556 and 62.5-64 C, Richardson, A. et. al., Journal of Organic Chemistry,1960, 25, 1138); 1H NMR (300 MHz, CDCl3) delta 8.76 (dd, 1 H, J = 4.23, 1.75 Hz), 8.06 (dd, 1 H, J = 8.20, 1.96), 7.37-7.30 (om's, 2 H), 7.15 (dd, 1 H, J = 8.01, 1.30), 6.92 (dd, 1 H, J = 7.51, 1.42), 4.98 (br s, 2 H, N-H2); MS (EI) 144; Analysis: Calculated C 74.98 H 5.59 N 19.43 Found C 74.88 H 5.67 N 19.26.
With potassium carbonate; trifluoroacetic acid;copper(I) iodide; In NH3-solution; water; N,N-dimethyl-formamide;
(i) 1-(4-Amino-3-fluoro-phenyl)-1H-pyrazin-2-one A mixture of 2 g 2-Fluoro-4-iodo-phenylamine, 1 g sodium salt of 1 H-Pyrazin-2-one, 1,3 g potassium carbonate, 612 mg 8-hydroxyquinoline and 804 mg copper(I) iodide in 20 ml DMF was carefully degassed under an atmosphere of argon. The reaction mixture was heated to 130 C in a microwave reactor for 120 min. 10 mL of 14% NH3-solution were added and the mixture was stirred for 1 h. 20 mL water were added and the mixture was extracted with ethylacetate. The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 180 mg MS (ES+): m/e= 206.
With potassium carbonate; trifluoroacetic acid;copper(I) iodide; In water; N,N-dimethyl-formamide;
(ii) 5-(2-Oxo-2H-pyrazin-1-yl)-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester A mixture of 712 mg <strong>[261732-38-1]5-Bromo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester</strong>, 338 mg sodium salt of 1H-Pyrazin-2-one, 363 mg potassium carbonate, 173 mg 8-hydroxyquinoline and 227 mg copper(I) iodide in 10 ml DMF was carefully degassed under an atmosphere of argon. The reaction mixture was heated to 120 C for 6h. 4 mL of 14% NH3-solution was added and the mixture was stirred for 1 h. 20 mL water were added and the mixture was extracted with ethylacetate. The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by preparative HPLC (C18 reverse phase column, elution with a H2O/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 237 mg MS (ES+): m/e= 314.
Compound according to Example 15 7-(Morpholin-4-yl-pyrazin-2-yl-methyl)-quinolin-8-ol The preparation was carried out analogously to the method described for Example Compound 6 using: 8-hydroxyquinoline (145 mg, 1.0 mmol) pyrazine-2-carbaldehyde (108 mg, 1.0 mmol) and morpholine (79 mul, 0.9 mmol) in dioxane (2 ml). Purification was carried out by means of preparative HPLC to give Example Compound 15 (91 mg, 28percent).
5-(5,6-dimethylbenzothiazol-2-yldiazenyl)-8-hydroxyquinoline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
General procedure: 2 mmol heterocyclic amines were dissolved in hot glacial aceticacid-propionic acid mixture (2:1, 6.0 mL) and was rapidly cooled inan ice-salt bath to-5 C. The liquor was then added in portions during30 min to a cold solution of nitrosyl sulfuric acid (prepared fromsodiumnitrite (0.15 g) and concentrated sulfuric acid, 98% (3mL at 50 C)). Themixturewas stirred for an additional 2 h at 0 C. Excess nitrous acidwasdestroyed by the addition of urea. The resulting diazonium salt wascooled in ice-salt bath. After diazotization was complete the azo liquorwas slowly added to vigorously stirred solution of 8-hydroxyquinoline(2 mmol, 0.29 g) in potassium hydroxide (2.0 × 10-3 mol, 0.112 g)and water (2 mL). The solution was stirred at 0-5 C for 2 h. After thatthe pH of the reaction mixture was maintained at 4-6 by the simultaneousaddition of saturated sodium carbonate solution. The mixturewas stirred for 1 day at room temperature. The resulting solid was filtered,washed with cold water and dried. The obtained compoundswere purified by crystallization using ethanol and then analyzed. Theyields of the dyes are in range of 54-78%. Characterization data areshown below. Preparation of 5-(5,6-dimethylbenzothiazol-2-yldiazenyl)-8-hydroxyquinoline (II-11) This dye was obtained from <strong>[29927-08-0]2-amino-5,6-dimethylbenzothiazole</strong> and 8-hydroxyquinoline as claret red powder (yield: 0.36 g, 54%; m.p: 264-265 C). IR (KBr): numax: 3288 (quinoline OH), 3050 (aromatic CH), 2921, 2851 (aliphatic CH), 1573, 1510 (C=C), 1234 (C-O) cm- 1; 1H NMR (CDCl3): delta 9.25 (d,1H), 8.85 (d,1H), 8.28 (d,1H), 7.85 (s,1H), 7.62 (m,1H), 7.57 (s,1H), 7.24 (d,1H), 2.33 (s,6H). Anal. calcd. for C18H14N4OS (334.39): C, 64.65; H, 4.22; N, 16.75; S, 9.59. Found C, 64.37; H, 4.18; N, 16.70; S, 9.46. MS: (m/z, 70 eV): 335 (M + 1)+.
With Di-tert-butyl acetylenedicarboxylate; In neat (no solvent); at 100℃; for 0.116667h;Microwave irradiation; Green chemistry;
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 1-methyl-1H-imidazole; In neat (no solvent); at 100℃; for 0.116667h;Microwave irradiation; Green chemistry;
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.
General procedure: 5-Methoxysalicylaldehyde(0.1 mmol, 15.2 mg) and <strong>[42826-42-6]pivalohydrazide</strong> (0.1 mmol,11.6 mg) were dissolved in methanol (15 mL). Themixture was stirred at room temperature for 30 min togive a colorless solution. To the solution was addedwith stirring a methanolic solution (10 mL) of 8-hydroxyquinoline (0.1 mmol, 14.5 mg) andVO(Acac)2 (0.1 mmol, 26.5 mg). The mixture was furtherstirred at room temperature for 30 min to give adeep brown solution. After keeping the solution in airfor a few days, brown block-shaped single crystals,suitable for X-ray crystal structure determination,were obtained. The crystals were isolated by filtrationand dried in a vacuum desiccator containing anhydrousCaCl2. The yield was 62%.IR data (KBr; numax, cm-1): 3049, 2962, 2929, 1600,1548, 1467, 1402, 1322, 1270, 1222, 1163, 1102, 1023,969, 834, 789, 752, 626, 554, 482. UV-Vis data in acetonitrile(lambda, nm (epsilon, M-1 cm-1)): 242 (21230), 335(3850), 515 (2930). 1H NMR (300 MHz; d6-DMSO;delta, ppm): 9.20 (s., 1H, ArH), 8.55 (s., 1H, CH=N),8.35 (d., 1H, ArH), 7.75-7.55 (m., 3H, ArH), 7.43 (s.,1H, ArH), 7.09 (d., 1H, ArH), 6.95 (d., 1H, ArH),6.75 (d., 1H, ArH), 3.76 (s., 3H, OCH3), 0.78 (s., 9H,CH3). For C22H22N3O5VAnal. calcd., %: C, 57.52; H, 4.83; N, 9.15.Found, %: C, 57.37; H, 4.96; N, 9.07.
General procedure: 5-Methoxysalicylaldehyde(0.1 mmol, 15.2 mg) and <strong>[42826-42-6]pivalohydrazide</strong> (0.1 mmol,11.6 mg) were dissolved in methanol (15 mL). Themixture was stirred at room temperature for 30 min togive a colorless solution. To the solution was addedwith stirring a methanolic solution (10 mL) of 8-hydroxyquinoline (0.1 mmol, 14.5 mg) andVO(Acac)2 (0.1 mmol, 26.5 mg). The mixture was furtherstirred at room temperature for 30 min to give adeep brown solution. After keeping the solution in airfor a few days, brown block-shaped single crystals,suitable for X-ray crystal structure determination,were obtained. The crystals were isolated by filtrationand dried in a vacuum desiccator containing anhydrousCaCl2.
(E)-5-[[4-(1H-imidazol-1-yl)phenyl]diazenyl]quinolin-8-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
General procedure: A mixture of aniline derivative 1a-1e (1 mmol) and 1 cm3concentrated hydrochloric acid was thoroughly stirred atroom temperature for 15 min and then cooled to 0 C. Asolution containing 0.069 g sodium nitrite (1 mmol) in 10 cm3 water was added dropwise to the initial mixtureduring 40 min. An aqueous solution of aromatic nucleophile(1 mmol) in NaOH 10% (5 cm3) was then addedand the resulted mixture was stirred for 1 h at 0 C. Theprecipitated solid was filtered, washed with water and dried in air. The products 2a-2c, 2e, 2f, 2m, and 2o were purifiedby recrystallization in ethanol, but preparative TLC (nhexane-EtOAc, 4:1) was applied for purification of products2d, 2g-2l, 2n, and 2p.
(E)-5-[[4-(1H-pyrazol-1-yl)phenyl]diazenyl]quinolin-8-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
General procedure: A mixture of aniline derivative 1a?1e (1 mmol) and 1 cm3concentrated hydrochloric acid was thoroughly stirred atroom temperature for 15 min and then cooled to 0 C. Asolution containing 0.069 g sodium nitrite (1 mmol) in 10 cm3 water was added dropwise to the initial mixtureduring 40 min. An aqueous solution of aromatic nucleophile(1 mmol) in NaOH 10percent (5 cm3) was then addedand the resulted mixture was stirred for 1 h at 0 C. Theprecipitated solid was filtered, washed with water and dried in air. The products 2a?2c, 2e, 2f, 2m, and 2o were purifiedby recrystallization in ethanol, but preparative TLC (nhexane?EtOAc, 4:1) was applied for purification of products2d, 2g?2l, 2n, and 2p.
With bromine; In chloroform; at 20℃; for 48h;Darkness;
General procedure: To synthesize brominated 8-substituted quinolines (5-10) experimental procedures were repeated in literature [19]. In brief, to a solution of 8-substituted quinoline 2-4 (2 mmol, 1 eq) in distilled CHCl3 (15 mL) was added a solution of molecular bromine (different eqivalents) in CHCl3 over 10 min in the dark at ambient temperature and stirred for 2 days. The reaction was monitored by TLC; after completion of the reaction, the organic layer was washed with 5% NaHCO3 (3 × 20 mL), dried over Na2SO4, and concentrated under reduced pressure. The products was isolated by alumina column, eluting with AcOEt/hexane (1:5, 150 mL).
(trans)-methyl 3-(quinolin-8-yloxy)cyclobutanecarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66%
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 72h;
Triphenylphosphine (5.42 g, 20.7 mmol) was added to a solution of quinolin-8-ol (2.00 g, 13.8 mmol) in tetrahydrofuran (40 mL). The reaction mixture was cooled to 0 C, and (cis)- methyl 3-hydroxycyclobutanecarboxylate (2.15 g, 16.5 mmol) was added, followed by DIAD (4.0 mL, 21 mmol). The reaction mixture was then warmed to room temperature, stirred for 3 days, and diluted with water and EtOAc. The mixture was partitioned, and the aqueous layer was extracted with EtOAc. The organics were washed with water, dried over sodium sulfate, filtered, and concentrated. The residue was purified on silica gel eluting with a 30%-70% EtOAc-hexanes gradient to give the title compound as a thick oil (2.4 g, 66%). 1H NMR (400 MHz, CD3SOCD3) delta 2.74-2.84 (m, 2 H), 2.86-2.96 (m, 2 H), 3.23-3.31 (m, 1 H), 3.78 (s, 3 H), 5.14-5.23 (m, 1 H), 6.91 (dd, J = 7, 2 Hz, 1 H), 7.41 -7.52 (m, 3 H), 8.16 (dd, J = 8, 2 Hz, 1 H), 8.98 (dd, J = 4, 2 Hz, 1 H); LC-MS (LC-ES) M+H = 258.
With bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate salt; potassium iodide; In ethanol; at 20℃; for 1.16667h;
General procedure: To a 25-mL flask containing a stirred solution of pyridine-N-oxide (1 mmol, 0.095 g) in EtOH (3 mL), Hendrickson reagent (1 mmol, 0.839 g), and KI (2 mmol, 0.336 g) were added. The mixture was stirred magnetically at room temperature, and monitored by TLC. Upon completion of the reaction, the solvent was evaporated, and then saturated sodium bicarbonate solution (10 mL) was added. The product was extracted with chloroform (3 × 5 mL), and dried over anhydrous MgSO4. The filtrate was evaporated, and pyridine (0.059 g, 75percent) was obtained as the sole product.
7-((3-fluoro-5-(trifluoromethyl)phenyl)(6-methylpyridin-2-ylamino)methyl)quinolin-8-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
35%
With formic acid; In acetonitrile; at 75℃;
General procedure: To a solution of 1 mmol aldehyde, 3 volume of acetonitrile and 1 equivalent volume of aminewere added to 0.6 equivalent of quinoline derivatives and 1% (v/v) formic acid. The reaction mixturewas stirred at higher temperature (75 C). The reaction was monitored by TLC (eluent: hexaneisomeric mixture:acetone). If the product precipitated, it was filtered, washed with hexane, and dried.If the reaction mixture was homogeneous, it was evaporated to dryness and was purified by columnchromatography (eluent: hexane:acetone from 20:1 to 4:1, v/v). The crude product was crystallizedfrom hexane/ethyl-acetate. The molecular structures were determined by means of 1D and 2D-NMRtechnologies (see Supplementary Materials)
7-((4-fluoro-3-(trifluoromethyl)phenyl)(6-methylpyridin-2-ylamino)methyl)quinolin-8-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With formic acid; In acetonitrile; at 75℃;
General procedure: To a solution of 1 mmol aldehyde, 3 volume of acetonitrile and 1 equivalent volume of aminewere added to 0.6 equivalent of quinoline derivatives and 1% (v/v) formic acid. The reaction mixturewas stirred at higher temperature (75 C). The reaction was monitored by TLC (eluent: hexaneisomeric mixture:acetone). If the product precipitated, it was filtered, washed with hexane, and dried.If the reaction mixture was homogeneous, it was evaporated to dryness and was purified by columnchromatography (eluent: hexane:acetone from 20:1 to 4:1, v/v). The crude product was crystallizedfrom hexane/ethyl-acetate. The molecular structures were determined by means of 1D and 2D-NMRtechnologies (see Supplementary Materials)
7-((2,4-bis(trifluoromethyl)phenyl)(6-methylpyridin-2-ylamino)methyl)quinolin-8-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
22%
With formic acid; In acetonitrile; at 75℃;
General procedure: To a solution of 1 mmol aldehyde, 3 volume of acetonitrile and 1 equivalent volume of aminewere added to 0.6 equivalent of quinoline derivatives and 1percent (v/v) formic acid. The reaction mixturewas stirred at higher temperature (75 C). The reaction was monitored by TLC (eluent: hexaneisomeric mixture:acetone). If the product precipitated, it was filtered, washed with hexane, and dried.If the reaction mixture was homogeneous, it was evaporated to dryness and was purified by columnchromatography (eluent: hexane:acetone from 20:1 to 4:1, v/v). The crude product was crystallizedfrom hexane/ethyl-acetate. The molecular structures were determined by means of 1D and 2D-NMRtechnologies (see Supplementary Materials)
7-((3-fluoro-5-(trifluoromethyl)phenyl)(4-methylpyrimidin-2-ylamino)methyl)quinolin-8-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
15%
With formic acid; In acetonitrile; at 75℃;
General procedure: To a solution of 1 mmol aldehyde, 3 volume of acetonitrile and 1 equivalent volume of aminewere added to 0.6 equivalent of quinoline derivatives and 1% (v/v) formic acid. The reaction mixturewas stirred at higher temperature (75 C). The reaction was monitored by TLC (eluent: hexaneisomeric mixture:acetone). If the product precipitated, it was filtered, washed with hexane, and dried.If the reaction mixture was homogeneous, it was evaporated to dryness and was purified by columnchromatography (eluent: hexane:acetone from 20:1 to 4:1, v/v). The crude product was crystallizedfrom hexane/ethyl-acetate. The molecular structures were determined by means of 1D and 2D-NMRtechnologies (see Supplementary Materials)
7-((4-fluoro-3-(trifluoromethyl)phenyl)(4-methylpyrimidin-2-ylamino)methyl)quinolin-8-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
25%
With formic acid; In acetonitrile; at 75℃;
General procedure: To a solution of 1 mmol aldehyde, 3 volume of acetonitrile and 1 equivalent volume of aminewere added to 0.6 equivalent of quinoline derivatives and 1% (v/v) formic acid. The reaction mixturewas stirred at higher temperature (75 C). The reaction was monitored by TLC (eluent: hexaneisomeric mixture:acetone). If the product precipitated, it was filtered, washed with hexane, and dried.If the reaction mixture was homogeneous, it was evaporated to dryness and was purified by columnchromatography (eluent: hexane:acetone from 20:1 to 4:1, v/v). The crude product was crystallizedfrom hexane/ethyl-acetate. The molecular structures were determined by means of 1D and 2D-NMRtechnologies (see Supplementary Materials)
7-((2,4-bis(trifluoromethyl)phenyl)(4-methylpyrimidin-2-ylamino)methyl)quinolin-8-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
16%
With formic acid; In acetonitrile; at 75℃;
General procedure: To a solution of 1 mmol aldehyde, 3 volume of acetonitrile and 1 equivalent volume of aminewere added to 0.6 equivalent of quinoline derivatives and 1percent (v/v) formic acid. The reaction mixturewas stirred at higher temperature (75 C). The reaction was monitored by TLC (eluent: hexaneisomeric mixture:acetone). If the product precipitated, it was filtered, washed with hexane, and dried.If the reaction mixture was homogeneous, it was evaporated to dryness and was purified by columnchromatography (eluent: hexane:acetone from 20:1 to 4:1, v/v). The crude product was crystallizedfrom hexane/ethyl-acetate. The molecular structures were determined by means of 1D and 2D-NMRtechnologies (see Supplementary Materials)
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