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Chemical Structure| 6563-13-9 Chemical Structure| 6563-13-9
Chemical Structure| 6563-13-9

6-Methoxyquinoline 1-oxide

CAS No.: 6563-13-9

4.5 *For Research Use Only !

Cat. No.: A596345 Purity: 97%

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Product Details of [ 6563-13-9 ]

CAS No. :6563-13-9
Formula : C10H9NO2
M.W : 175.18
SMILES Code : COC1=CC2=CC=C[N+]([O-])=C2C=C1
MDL No. :MFCD00009771
InChI Key :BWEGRKPOJXNZSK-UHFFFAOYSA-N
Pubchem ID :253821

Safety of [ 6563-13-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Calculated chemistry of [ 6563-13-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.1
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 51.6
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

34.69 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.6
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.53
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.48
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.69
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.29

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.76
Solubility 3.02 mg/ml ; 0.0172 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-0.83
Solubility 25.9 mg/ml ; 0.148 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.43
Solubility 0.654 mg/ml ; 0.00373 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.99 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

1.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

2.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.59

Application In Synthesis of [ 6563-13-9 ]

* 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.

  • Downstream synthetic route of [ 6563-13-9 ]

[ 6563-13-9 ] Synthesis Path-Downstream   1~29

  • 1
  • [ 5263-87-6 ]
  • [ 6563-13-9 ]
YieldReaction ConditionsOperation in experiment
97% With dihydrogen peroxide; In water; for 0.25h;Sonication; In a 50 mL round-bottom flask, 1.59 g of 6-methoxyquinoline and then 1.1 g of hydrogen peroxide (35% by mass) were successively added.5% mass fraction of perfluorosulfonic acid resin, 10 ml of water as a solvent, and the resulting mixture in an ultrasonic reaction apparatus at 60 W/The reaction was performed for 15 minutes under 20 KHz ultrasound. The resin catalyst in the reaction system was removed by filtration, and the reaction solvent was removed under reduced pressureWater, finally recrystallized to give 1.69 g of 6-methoxyquinoline nitrous oxide in 97% yield.
90% With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; for 24h; General procedure: To a solution of the corresponding quinoline substrate (5 mmol) in CH2Cl2 (30 mL), m-CPBA (7.5 mmol, 1.5 equiv) was added at 0 C. The reaction mixture was allowed to stir at room temperature for 24 h. Next, saturated aq NaHCO3 solution (100 mL) was added to the reaction mixture. Then, the mixture was extracted with CH2Cl2 (3 × 50 mL) and the organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to obtain the pure quinoline N-oxide (70-90% yield).
82% With dihydrogen peroxide; In acetic acid; at 100℃; for 2h; 6-Methoxy quinoline (15 g, 0.094 mol) was dissolved in acetic acid (97 ml) and treated with hydrogen peroxide (37 ml). The mixture was stirred to 100 C. for 2 hours. After evaporation to dryness 100 ml of water was added to the residue until a precipitate appears. Filtration and washing with water gives a yellow precipitate that is dried under vacuum to yield 13.5 g of the title compound as a light yellow solid (82%). MS (m/e): 176.3 (M+H)+.
55% To a solution of 6- methoxyquinoline (2.00 g, 12.6 mmol) in AcOH (10 mL) was added Η202 (30% in water, 1.9 mL, 18.9 mmol), the mixture was heated to 70 C for 21 hours. The mixture was basified with 2M NaOH to pH 8-9 and extracted with CH2C12 (200 mL), the combined organic layer was washed with brine (50 mL), dried over Na2S04, filtered and concentrated to give the crude product, which was purified by silica gel column (EtOAc / MeOH=10 / 1) to give 6- methoxyquinoline 1-oxide (1.20 g, 55%) as a solid.
55% To a solution of 6- methoxyquinoline (2.00 g, 12.6 mmol) in AcOH (10 mL) was added H202 (30% in water, 1.9 mL, 18.9 mmol), the mixture was heated to 70 C for 21 hours. The mixture was basified with 2M NaOH to pH 8-9 and extracted with CH2C12 (200 mL), the combined organic layer was washed with brine (50 mL), dried over Na2S04, filtered and concentrated to give the crude product, which was purified by silica gel column (EtOAc / MeOH=10 / 1) to give 6- methoxyquinoline 1-oxide (1.20 g, 55%) as a solid.
With dihydrogen peroxide; In acetic acid; at 82℃; for 19h; A solution of 6-methoxyquinoline (11.21 g, 70 [MMOL)] in glacial acetic acid is treated dropwise with 30% hydrogen peroxide (15 mL) and then heated at [82C] for 19 hours. The reaction mixture is cooled, poured onto ice and carefully basified with concentrated ammonium hydroxide. The precipitate is collected, washed with hexane and dried in vacuo to provide the title compound (quantitative yield), which is used as such in the next step. MS [ (+) ES, m/z]: 176.1 [M+H] +
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; for 12h; General procedure: To a solution of the corresponding N-heterocycles (10.0 mmol) in CH2Cl2 (20 mL), m-chloroperoxybenzoic acid (m-CPBA, 20.0 mmol, 2.0 equiv) was added at 0 C. The reaction mixture was allowed to stir at room temperature for 12 h. Then saturated aqueous NaHCO3 (20 mL) was added. The aqueous was extracted with CH2Cl2 (10 mL x 3) and the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with EtOAc/n-hexene or EtOAc/MeOH to afford desired N-oxides.
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃;Inert atmosphere; General procedure: To a solution of 6-methylquinoline (270 µL, 2.0 mmol, 1.0 eq) in dry dichloromethane (4.0 mL), m-chloroperbenzoic acid (690 mg, 4.0 mmol, 2.0 eq) was added at 0 C under argon. The mixture was stirred overnight at room temperature, then diluted with dichloromethane and washed with potassium hydroxide (6 M). The organic layers were dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure. A mixture of the residue, molecular sieve (4 Å) and tetrabutylammonium bromide (967 mg, 3.0 mmol, 1.5 eq) in dry dichloromethane (200 mL) was stirred for 10 min at room temperature. p-Toluenesulfonic anhydride (979 mg, 3.0 mmol, 1.5 eq) was added and stirring was continued at room temperature overnight. The reaction mixture was filtered and the solvent was evaporated to dryness under reduced pressure. The crude product was purified by column chromatography (cyclohexane/chloroforme 10:15:11:1) to give 297 mg (1.34 mmol, 67%) of the analytically pure compound. C10H8BrN; MW: 222; 1H NMR (CDCl3, 400 MHz): δ 7.99-7.87 (m, 2H), 7.62-7.53 (m, 2H), 7.46 (d, J = 8.5 Hz, 1H), 2.52 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 147.3, 140,9, 137.9, 137.3, 132.9, 128.4, 127.1, 126.7, 125.8, 21.7.; MS (ESI): 223 (M+H)+.
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 0 - 20℃; General procedure: 77% 3-chloroperbenzoic acid (m-CPBA) (3 mmol) in CH2Cl2 (5 mL) was dropped into a solutionof quinoline derivatives (2 mmol) in CH2Cl2 (5 mL) cooled to 0 under vigorous magnetic stirringfor overnight. After the completion of this course, the reaction mixture was allowed up to roomtemperature and stirred overnight. An aqueous solution of saturated NaHCO3 was added to themixture to neutralize residual m-CPBA. The resulting mixture was extracted with CH2Cl2 (3 × 10mL). The organic phase was combined and washed with saturated NaCl solution (3 × 5 mL). The organiclayer was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure to givecrude products, which were purified by column chromatography (silica gel 200-300 mesh, AcOEt:MeOH (95:05) as eluent). The products were identified by 1H NMR and MS spectra and comparedto the previous literature.

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  • 2
  • [ 6563-13-9 ]
  • [ 13676-00-1 ]
YieldReaction ConditionsOperation in experiment
67% With acetic anhydride; for 2h;Reflux; A solution of 6- methoxyquinoline 1-oxide (300 mg, 1.71 mmol) in Ac20 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc (50 mL), the organic layer was washed with brine (10 mL), dried over Na2S04, filtered and concentrated to give the crude product which was purified by silica gel column (PE / EtOAc=l / 2) to give 6-methoxyquinolin-2-ol (200 mg, yield 67%).
67% With acetic anhydride; for 2h;Reflux; A solution of 6- methoxyquinoline 1-oxide (300 mg, 1.71 mmol) in Ac20 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc (50 mL), the organic layer was washed with brine (10 mL), dried over Na2S04, filtered and concentrated to give the crude product which was purified by silica gel column (PE / EtOAc=l / 2) to give 6-methoxyquinolin-2-ol (200 mg, yield 67%).
  • 3
  • [ 6563-13-9 ]
  • [ 13676-00-1 ]
YieldReaction ConditionsOperation in experiment
95% With zinc(II) oxide; In diethyl ether; for 2h;Irradiation; Accurately weigh the reaction substrate 6-methoxyquinoline-N-oxide (175.1 mg, 1.0 mmol) and zinc oxide (3 mol%, 2.4 mg) into a quartz reactor, add 2.0 ml of ether, in air conditions After reacting for 2 hours under a xenon lamp irradiation, the ether was removed by a rotary evaporator, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2:1). product. The product was a white powdery solid in a yield of 95% (166.3 mg).
In acetic anhydride; at 75℃; for 18h; The crude <strong>[6563-13-9]6-methoxyquinoline 1-oxide</strong> of Step A (70 [MMOL)] is suspended in acetic anhydride (70 mL) and heated at [75C] under nitrogen for 18 hours. The mixture is poured onto ice and carefully basified with ammonium hydroxide. The precipitate is collected, washed with hexane and dried. The solid is suspended in dichloromethane, filtered and dried to provide the title compound (5.136 g). Additional material (1.79 g) is obtained by flash chromatography of the mother liquors on silica gel [MARCK-60] using a gradient of methanol (1-5%) in hexane-ethyl acetate (1: [1).] MS [(+) ES, m/z]: 176.1 [M+H] +
With acetic anhydride; In tert-butyl alcohol; at 80℃; for 66h; Acetic anhydride (0.94 mL, 10 mmol) was added to a solution of <strong>[6563-13-9]6-methoxyquinoline N-oxide</strong> (1.75 g, 10 mmol, see: Dimsdale, M. J. J. Het. Chem. 1979, 16, 1209) in tertiary butanol (10 mL). The resulting mixture was heated at 80 C for 18 h then additional acetic anhydride (0.94 mL, 10 mmol) was added. The mixture was heated at 80 C for an additional 2 days. The reaction mixture cooled to rt and was diluted with EtOAc and water. The organic phase was collected and washed with sat. NaHCO3, dried and concentrated to afford 6-methoxy-1H-quinolin-2-one (0.45 g). This material was converted to the title compound using the method described in Preparation 23.
  • 5
  • [ 6563-13-9 ]
  • [ 103753-39-5 ]
YieldReaction ConditionsOperation in experiment
19.2 G of benzoyl chloride are added dropwise to a suspension of 46.5 G of silver nitrate in 80 mi of dichloromethane at 15C. The reaction mixture is stirred at room temperature for 0.5 h and at boiling temperature for 1 h. The precipitate is filtered off and the filtrate is dropped to a solution of 24.0 G of 6- METHOXYQUINOLINE-1-OXIDE (compound E3) in 80 ml of DICHLOROMETHANE at 10 C. The reaction mixture is refluxed for 1.5 h. After cooling to room temperature, the reaction mixture is diluted with 200 ML of di- CHLOROMATHANE and EXTRACTED TWO TIMES. EACH WITH 200 ML OF HALFSATURATED AQUEOUS SODIUM HYDROGEN- carbonate SOLUTION. ; THE ORGANIWLAYER. IS DRIED OVER MAGNESIUM SULFATE, FIITERED and evaporated in vacuo. The residue is RECRYSTAIIIZED from ethyl-acetate. to give 8. 2 g of the title compound as. yellow crystals. EF: C, OH3N204 TLC: Rf = 0.73 (ethyl acetate) MS: calc. : 220.2 fnd: 220. 0 [MI
  • 6
  • [ 6563-13-9 ]
  • [ 506-64-9 ]
  • [ 5467-79-8 ]
YieldReaction ConditionsOperation in experiment
82% With benzoyl chloride; In chloroform; at 20℃; for 18h;Heating / reflux; 6-Methoxy-quinoline-1-oxide (13.48 g, 0.076 mol) in 30 ml chloroform was treated with 3.87 g (0.028 mol) of benzoyl chloride and 3.65 g (0.0 27 mol) of silver cyanide. The mixture was stirred for 4 hours at room temperature and stirred to reflux for additional 14 h. After evaporation of the solvent to half volume the mixture was cooled to 0 C. and a precipitate of silver salt appeared. The mixture was filtered and the solution was concentrated and the solid residue was washed in diethyl ether and dried under vacuum to yield 11 g (82%) of the title compound as light brown solid. MS (m/e)=185.3 (M+H)+.
  • 7
  • [ 6563-13-9 ]
  • [ 141-97-9 ]
  • [ 125448-15-9 ]
YieldReaction ConditionsOperation in experiment
4.5 g (32%) With hydrogenchloride; In acetic anhydride; Step 1 Ethyl 6-methoxy-2-quinolylacetate Ethyl acetoacetate (10.0 g) was added to 6-methoxyquinoline-1-oxide (10.0 g, 57.14 mmol) in acetic anhydride (15 mL) and the reaction mixture was heated at 40 C. for 6 h. The reaction mixture was poured in to an ice-cold solution of 10% HCl (100 mL). After 1 h, the reaction mixture was extracted with dichloromethane (2*100 mL). The combined organic extracts were dried and concentrated to afford 4.5 g (32%) of the desired product as oil. 1H NMR (CD3OD) δ8.20(d, 1H, J=8.5 Hz), 7.86 (d, 1H, J=9.4 Hz), 7.44 (d, 1H, J=8.6 Hz), 7.37 (m, 1H), 7.24 (d, 1H, J=8.9 Hz), 4.16 (q, 2H, J=7.1 Hz), 3.97 (s, 2H), 3.91 (s, 3H), 1.23 (t, 3H, J=7.1 Hz). Anal. Calcd for C14H15NO3: 246.1130 (M+H). Found, Mol. Wt, 246.1144 (M+H, HRMS).
  • 8
  • [ 6563-13-9 ]
  • [ 13676-02-3 ]
YieldReaction ConditionsOperation in experiment
2.5 g (46%) With trichlorophosphate; In chloroform; Step 1a A solution of <strong>[6563-13-9]6-methoxyquinoline N-oxide</strong> (5.0 g, 29 mmol) in CHCl3 (30 mL) was treated by slow addition of POCl3 (5.3 mL, 57 mmol) at 0 C. The mixture was heated at 80 C. for 14 hours. The mixture was cooled and poured onto ice. After stirring for 30 min., the aqueous layer was adjusted to pH 9 by Na2CO3 addition. The mixture was extracted with CH2Cl2. The organic layer was worked-up. HPLC (1:10 EtOAc/hexane) gave 2.5 g (46%) of 2-chloro-6-methoxyquinoline as a white solid, (M+) 193(100).
  • 9
  • [ 106-39-8 ]
  • [ 6563-13-9 ]
  • 6-methoxy-2-(4-chlorophenyl)quinoline N-oxide [ No CAS ]
  • 10
  • [ 108-86-1 ]
  • [ 6563-13-9 ]
  • [ 61845-41-8 ]
  • 11
  • [ 104-92-7 ]
  • [ 6563-13-9 ]
  • [ 1127561-67-4 ]
  • 12
  • [ 6563-13-9 ]
  • [ 106-38-7 ]
  • [ 1127561-65-2 ]
  • 13
  • [ 6563-13-9 ]
  • [ 7677-24-9 ]
  • [ 5467-79-8 ]
YieldReaction ConditionsOperation in experiment
92% With tetrachloromethane; potassium carbonate; phosphonic acid diethyl ester; In dimethyl sulfoxide; at 20℃; for 4h; 6-methyl-quinoline-N-oxide (0.175 g, 1 mmol), trimethyl cyanosilane (0.119 g, 1.2 mmol), diethyl H-phosphite (0.276 g, 2 mmol), carbon tetrachloride (0.308g, 2mmol), K2CO3(0.276g, 2mmol), 10mL of DMSO in a 50mL three-necked flask, and reacted at room temperature for 4h. After the reaction was completed, 20ml of water was added and extracted with dichloromethane. The organic phases were combined, dried, filtered, and the solvent was removed under reduced pressure. Column chromatography (petroleum ether / ethyl acetate, V / V = 5: 1), the target compound was obtained as a white powder, with a yield of 92%, and the structural formula was as follows:
  • 14
  • [ 6563-13-9 ]
  • [ 2398-37-0 ]
  • [ 476159-12-3 ]
YieldReaction ConditionsOperation in experiment
47% To 231 mg (9.63 mmol, 6 eq) of purified magnesium in 10 ml of dry ether are added two crystals of iodine and 1.5 g (8.02 mmol, 5 eq) of bromoanisole dissolved in 10 ml of dry ether. The reaction mixture is boiled under reflux and under nitrogen atmosphere at 30 C. for 2 h.Coupling: 281 mg (1.60 mmol, 1 eq) of 6-methoxyquinoline-N-oxide dissolved in 80 ml of toluene is added to the Grignard mixture, and the mixture is heated at 90 C. for 2 h. After cooling the round-bottom flask, the reaction mixture is added on ice, and after the ice is molten, 2 N hydrochloric acid and water are added until the precipitate formed has dissolved. The water phase is washed with ether and made alkaline with KOH. After extraction with chloroform, the combined organic phases are dried over magnesium sulfate, filtered, and the solvent is removed in vacuum on a rotary evaporator. Purification was performed by means of column chromatography with hexane/ethyl acetate 95/5 as the eluent to obtain the desired product in a yield of 47% (199 mg).C17H15NO2; MW 265; 1H-NMR (CDCl3): δ 7.91 (d, J=1.5 Hz, 1H), 7.89 (s, 1H), 7.62 (d, J=8.8 Hz, 1H); 7.57 (t, J=2.4 Hz, 1H), 7.50 (d, J=7.9 Hz, 1H), 7.24 (t, J=7.9 Hz, 1H), 7.20 (dd, J=2.7 Hz, J=9.1 Hz, 1H), 6.89 (d, J=2.7 Hz, 1H), 6.82 (dd, J=2.7 Hz, J=8.2 Hz, 1H), 3.75 (s, 3H), 3.74 (s, 3H); 13C-NMR (CDCl3): δ 160.1, 157.7, 154.8, 144.3, 141.3, 135.5, 131.1, 129.8, 128.3, 122.4, 119.8, 119.4, 115.0, 112.5, 105.0, 55.5, 55.4; IR: 2964, 2839, 1621, 1600, 1583, 1559, 1478, 1455, 1430 1/cm; MS (ESI): 266 (M+H)+
  • 15
  • [ 109-04-6 ]
  • [ 6563-13-9 ]
  • [ 1355019-53-2 ]
  • 16
  • [ 6563-13-9 ]
  • [ 476161-59-8 ]
YieldReaction ConditionsOperation in experiment
General procedure: To a solution of 6-methylquinoline (270µL, 2.0mmol, 1.0eq) in dry dichloromethane (4.0mL), m-chloroperbenzoic acid (690mg, 4.0mmol, 2.0eq) was added at 0C under argon. The mixture was stirred overnight at room temperature, then diluted with dichloromethane and washed with potassium hydroxide (6M). The organic layers were dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure. A mixture of the residue, molecular sieve (4Å) and tetrabutylammonium bromide (967mg, 3.0mmol, 1.5eq) in dry dichloromethane (200mL) was stirred for 10min at room temperature. p-Toluenesulfonic anhydride (979mg, 3.0mmol, 1.5eq) was added and stirring was continued at room temperature overnight. The reaction mixture was filtered and the solvent was evaporated to dryness under reduced pressure. The crude product was purified by column chromatography (cyclohexane/chloroforme 10:15:11:1) to give 297mg (1.34mmol, 67%) of the analytically pure compound. C10H8BrN; MW: 222; 1HNMR (CDCl3, 400MHz): δ 7.99-7.87 (m, 2H), 7.62-7.53 (m, 2H), 7.46 (d, J=8.5Hz, 1H), 2.52 (s, 3H); 13CNMR (CDCl3, 100MHz): δ 147.3, 140,9, 137.9, 137.3, 132.9, 128.4, 127.1, 126.7, 125.8, 21.7.; MS (ESI): 223 (M+H)+.
  • 17
  • [ 6563-13-9 ]
  • [ 13676-02-3 ]
  • [ 4295-04-9 ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate; In dichloromethane; N,N-dimethyl-formamide; at 0 - 25℃;Inert atmosphere; General procedure: To a stirred solution of the appropriate azine N-oxides in anhydrous CH2Cl2 (0.1M) at 0 C is added POCl3 (1.2 equiv) followed by dropwise addition of DMF (0.5 equiv) under argon. The resulting reaction mixture was warmed to 25 C and stirred for several hours until the reaction is complete as indicated by TLC. Saturated aqueous sodium carbonate solution is added to the reaction mixture slowly to adjust the pH to 7~8. The resulting mixture is separated and the aqueous phase is extracted with CH2Cl2 thoroughly. The organic phase is combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which is purified by flash column chromatography using PE/EA (80:1) as eluent.
  • 18
  • [ 6563-13-9 ]
  • [ 7357-70-2 ]
  • (2Z)-2-cyano-2-(6-methoxyquinolin)-2(1H)-ylidene-ethanethioamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With acetic anhydride;Reflux; General procedure: The title compounds 1a-d were prepared from the reaction ofthe appropriate quinoline N-oxide (10 mmol) with the desired activemethylene nitrile in refluxing Ac2O. The adopted procedurefollowed the earlier protocol employed by Hamana, Klemm andOchiai for related derivatives [15,17,19]. Each product was recrystallizedfrom acetonitrile. The IR and NMR spectroscopic data aresummarized in Table 1. Yield of 1a: 89% (2.0 g). Anal. Calcd. (found)for C12H9N3S: C, 63.41 (63.33); H, 3.99 (4.11). Yield of 1b: 81%(1.8 g). Anal. Calcd (found) for C13H9N3O: C, 69.50 (69.73); H,4.06 (4.13). Yield of 1c: 76% (2.0 g). Anal. Calcd. (found) forC15H14N2O3: C, 66.66 (66.55); H, 5.22 (5.22). Yield of 1d: 81%(2.1 g). Anal. Calcd (found) for C13H11N3OS: C, 60.68 (60.90); H,4.31 (4.35).
  • 19
  • [ 6563-13-9 ]
  • [ 109-77-3 ]
  • 6-methoxyquinolin-2(1H)-ylidene-propanedinitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With acetic anhydride;Reflux; General procedure: The title compounds 1a-d were prepared from the reaction ofthe appropriate quinoline N-oxide (10 mmol) with the desired activemethylene nitrile in refluxing Ac2O. The adopted procedurefollowed the earlier protocol employed by Hamana, Klemm andOchiai for related derivatives [15,17,19]. Each product was recrystallizedfrom acetonitrile. The IR and NMR spectroscopic data aresummarized in Table 1. Yield of 1a: 89% (2.0 g). Anal. Calcd. (found)for C12H9N3S: C, 63.41 (63.33); H, 3.99 (4.11). Yield of 1b: 81%(1.8 g). Anal. Calcd (found) for C13H9N3O: C, 69.50 (69.73); H,4.06 (4.13). Yield of 1c: 76% (2.0 g). Anal. Calcd. (found) forC15H14N2O3: C, 66.66 (66.55); H, 5.22 (5.22). Yield of 1d: 81%(2.1 g). Anal. Calcd (found) for C13H11N3OS: C, 60.68 (60.90); H,4.31 (4.35).
  • 20
  • [ 6563-13-9 ]
  • [ 105-56-6 ]
  • ethyl (2Z)-cyano-6-methoxyquinolin-2(1H)-ylidene-ethanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With acetic anhydride;Reflux; General procedure: The title compounds 1a-d were prepared from the reaction ofthe appropriate quinoline N-oxide (10 mmol) with the desired activemethylene nitrile in refluxing Ac2O. The adopted procedurefollowed the earlier protocol employed by Hamana, Klemm andOchiai for related derivatives [15,17,19]. Each product was recrystallizedfrom acetonitrile. The IR and NMR spectroscopic data aresummarized in Table 1. Yield of 1a: 89% (2.0 g). Anal. Calcd. (found)for C12H9N3S: C, 63.41 (63.33); H, 3.99 (4.11). Yield of 1b: 81%(1.8 g). Anal. Calcd (found) for C13H9N3O: C, 69.50 (69.73); H,4.06 (4.13). Yield of 1c: 76% (2.0 g). Anal. Calcd. (found) forC15H14N2O3: C, 66.66 (66.55); H, 5.22 (5.22). Yield of 1d: 81%(2.1 g). Anal. Calcd (found) for C13H11N3OS: C, 60.68 (60.90); H,4.31 (4.35).
  • 21
  • [ 110-89-4 ]
  • [ 6563-13-9 ]
  • [ 1581686-88-5 ]
YieldReaction ConditionsOperation in experiment
66% In toluene; at 80℃; General procedure: General procedure: A mixture of N-Oxide (0.5 mmol), secondary amine (2.5 mmol, 5 equiv),Cu-MnO (15mg) were taken in a carousel screw cap reaction tube equipped with a cross shapestirring bar. 1 mL toluene was added over it and the tube was sealed with the Teflon screw cap andstirred at 80C for 12-18 h. The reaction is monitored by TLC, upon the completion, the reactionmixture is cooled to room temperature and filtered through a plug of a celite, the filtrate wasconcentrated and evaporated to dryness in a rotary evaporator. The crude residue was purified byflash column chromatography (40:60/ Hexane : Ethyl acetate) to isolate the desired product.
  • 23
  • [ 6563-13-9 ]
  • [ 122-52-1 ]
  • [ 1623118-30-8 ]
YieldReaction ConditionsOperation in experiment
75.7% General procedure: To a solution of pyridine N-oxide (200 mg, 2.1 mmol) in anhydrous methylene chloride (10 mL)under argon atmosphere was added ethyl chloroformate (0.6 mL, 3 eq.) and the solution was stirred for 10 min at rt. And then triethyl phosphite (1.09 mL, 3 eq.) was added dropwiseto the reaction solution. The resulting solution was stirred for 30 min at rt, diluted with 20 mL of methylene chloride and washed with saturated NaHCO3 (30 mL), water (30 mL× 2) and brine (30 mL). The organic layer was dried with anhydrous MgSO4 and chromatographed on silica gel using ethyl acetate to give diethyl pyridin-2-ylphosphonate 2a in 94.2 % isolated yield.
  • 24
  • [ 6563-13-9 ]
  • [ 6773-29-1 ]
  • 8-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-6-methoxyquinoline N-oxide [ No CAS ]
  • 25
  • [ 6563-13-9 ]
  • 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one [ No CAS ]
  • 6-methoxy-8-[(triisopropylsilyl)ethynyl]quinoline N-oxide [ No CAS ]
  • 27
  • [ 273-53-0 ]
  • [ 6563-13-9 ]
  • 6-methoxy-2-(2-benzoxazolyl)quinoline [ No CAS ]
  • 28
  • [ 95-16-9 ]
  • [ 6563-13-9 ]
  • 6-methoxy-2-(2-benzothiazolyl)quinoline [ No CAS ]
  • 29
  • [ 6563-13-9 ]
  • [ 873-55-2 ]
  • 6-methoxy-2-(phenylsulfonyl)quinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With pyridine; tert.-butylhydroperoxide; iron(III) chloride hexahydrate; In water; acetonitrile; at 80℃; for 12h;Schlenk technique; General procedure: A Schlenk tube (35 ml) equipped with a magnetic bar was loaded with the solution of quinoline N-oxide 1 (0.5 mmol), sodium sulfinate 2 (1.0 mmol) and FeCl3*6H2O (20 mol%) in a mixture of CH3CN and H2O (5.0 ml, ca. 9:1 by volume). Then, TBHP (70% in decane, 1.0 mmol) and pyridine (1.0 mmol) were added to the solution dropwise via a syringe and the reaction mixture was stirred at 80 C for 12 h. After the completion of the reaction (monitored by thin layer chromatography), the mixture was washed with brine (15 ml) and then was extracted with dichloromethane (15 ml * 3). The organic phase was combined and then concentrated. The oily crude product was purified by column chromatography using silica gel (-200-300 mesh) as stationary phase and a mixture of petroleum and ethyl acetate as eluent to give the desired product in the noted yields.
70% With fluorosulfonyl fluoride; triethylamine; In dimethyl sulfoxide; at 40℃; for 16h; General procedure: To a 25 mL double-necked flask was added 0.3 mmol of quinoline N-oxide, 0.9 mmol of sodium sulfonate, 1.5 mmol of Et3N, 2.5 mL of DMSO, and bubble SO2F2 into the mixture using a balloon combined with syringe needle. The mixture stirred for 16 h at 40 C. The reaction mixture was diluted with 5 mL of water, and extracted with CH2Cl2 (3*20 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum. The crude product was further purified through flash column chromatography using the mixture of petroleum ether and ethyl acetate as eluent (PE : EA=10 : 1 - 4 : 1).
54% With ferric nitrate; In dimethyl sulfoxide; at 120℃; for 0.333333h;Microwave irradiation; General procedure: Quinoline N-oxides 1 (0.3 mmol), sodium arylsulfinates 2 (0.45 mmol) and Fe(NO3)3 (0.09 mmol) in DMSO (3.0 mL) were added to a microwave reaction tube (5.0 mL). The reaction mixture was heated at 120 C for 20 min under microwave irradiation. After reaction completion, the solvent was distilled under vacuum. Ethyl acetate (10 mL) was added to the residue, and washed with saturated sodium chloride solution (3 × 30 mL). The organic phase was dried over anhydrous NaSO4 and concentrated under vacuum. The crude product was purified by silica gel column chromatography to give the desired products 3 using ethyl acetate/petroleum ether (1:10 to 1:5) as the eluent. All compounds were confirmedby IR, 1H NMR, 13C NMR and MS.
 

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