* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Journal of Physical Chemistry B, 1997, vol. 101, # 14, p. 2650 - 2658
2
[ 578-67-6 ]
[ 10470-83-4 ]
Yield
Reaction Conditions
Operation in experiment
82%
With [bis(acetoxy)iodo]benzene In water; acetonitrile at 0℃; for 1 h; Inert atmosphere
A solution of iodobenzene diacetate (10.35mmol, 3.3g) in 12mL CH3CN: H2O (2:1) was added to quinolin-5-ol (3) (3.45mmol, 0.50g) at 0°C under N2 and stirred for 1h. After the reaction was completed, water (40mL) was added, and the solution was extracted with EtOAc (3×20mL). The organic phase was washed by brine and concentrated in vacuo to give 4 as a yellow solid, yield 82percent. MS (ESI) m/z = 160 [M+H]+.
Reference：
[1] Tetrahedron Letters, 1990, vol. 31, # 34, p. 4871 - 4872
[2] Organic and Biomolecular Chemistry, 2011, vol. 9, # 13, p. 4959 - 4976
[3] European Journal of Medicinal Chemistry, 2018, vol. 154, p. 199 - 209
[4] Synthetic Communications, 1999, vol. 29, # 18, p. 3063 - 3066
3
[ 13207-66-4 ]
[ 10470-83-4 ]
Yield
Reaction Conditions
Operation in experiment
61%
With sodium dichromate; sulfuric acid In dichloromethane; water at 0℃; for 1 h;
To 0.80g (5.0mmol) of 5-amino-8-hydroxyquinoline in 150mL of CH2Cl2 at 0°C was added 150mL of a 5percent aqueous solution of H2SO4 followed by slow addition of a pre-cooled solution of 2.98g (10.0mmol) of sodium dichromate in 50mL of H2O at 0°C. The yellow solution became orange and biphasic. After 1h, the reaction was extracted with methylene chloride and washed with brine. The organic extract was dried over magnesium sulfate and filtered. The solvent was removed under reduced pressure to give a yellow solid. The solid was purified using silica gel column chromatography eluting 3:2 ethyl acetate–hexanes to afford 0.49g (61percent) of quinoline-5,8-dione. 1H NMR (400MHz, CDCl3) δ: 8.90 (d, J=4.6Hz, 1H), 8.71 (s, 1H), 8.41 (d, J=8.1Hz, 1H), 7.74 (dd, J=4.6, 8.1Hz, 1H), 7.06 (d, J=10.9Hz, 1H), 6.90 (d, J=10.9Hz, 1H). 13C NMR (100.17MHz, CDCl3) δ: 182.1, 180.7, 148.8, 147.2, 138.2, 138.1, 135.4, 129.0, 128.3.
Reference：
[1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 478 - 487
[2] Patent: US4492704, 1985, A,
[3] Chemische Berichte, 1884, vol. 17, p. 1645
4
[ 58868-41-0 ]
[ 10470-83-4 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1983, vol. 31, # 1, p. 341 - 343
[2] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 13, p. 3950 - 3952
[3] Patent: KR2015/80425, 2015, A, . Location in patent: Paragraph 0450-0453
5
[ 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
With methylene blue In methanol; water at 20℃; for 0.666667h; Irradiation; Flow reactor;
95%
With bis-[(trifluoroacetoxy)iodo]benzene In water; acetonitrile at 0 - 20℃; for 3h;
1.3. Quinoline-5,8-dione (12)
To a solution of bis(trifluoroacetoxy)iodobenzene (7000 mg, 16.0 mmol, 2.9 equiv.) in acetonitrile (12 mL) and water (6 mL) in the ice-water bath, 8-hydroxyquinoline (813 mg, 5.6 mmol) was added portionwise. The resulting mixture was then warmed to room temperature and stirred for 3 h and insured all starting material had been consumed, acetonitrile evaporated under reduced pressure; the aqueous layer was extracted with ethyl acetate three times, and the residue was purified by column chromatography with a mixed eluent of petroleum ether and ethyl acetate (5:1, v/v) resulting in compound 12 (852 mg, 95%). mp. 129.1 - 130.3°C.
92%
With potassium dihydrogenphosphate; potassium nitrososulfonate In methanol for 2h; Ambient temperature;
89%
With bis-[(trifluoroacetoxy)iodo]benzene In water; acetonitrile
82%
With 5,10,15,20-tetrakisphenylporphyrin; oxygen In dichloromethane at 20℃; for 2.5h; Irradiation;
82%
With [bis(acetoxy)iodo]benzene; water In acetonitrile at 0℃; for 1h; Inert atmosphere;
1.4 (4) Preparation of quinoline-5,8-dione (compound 7)
Dissolve iodobenzene diacetic acid (10.35mmol, 3.3g) with a mixed solution of MeCN:H2O (8mL:4mL), 0°C, N2 protection Add 8-hydroxyquinoline (compound 6) (3.45mmol, 0.50g) under conditions, and after reacting for 1h, add 20mL of water to the reaction flask, It was extracted with ethyl acetate, the organic layers were combined and washed with saturated brine once, and dried over anhydrous sodium sulfate. Concentrate the filtrate after filtration After shrinking, a yellow solid was obtained with a yield of 82%.
70%
With oxygen In methanol; dichloromethane at 15℃; Irradiation;
44%
With potassium dihydrogenphosphate; Fremy's salt In water; acetone at 20℃; for 3.16667h;
2.1
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 - 40% ) 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, 44%).
44%
With potassium dihydrogenphosphate; potassiuim nitrosodisulfonate In water at 20℃; for 3h;
With dipyridinium dichromate In acetic acid at 34.9℃;
With methanol; potassium dihydrogenphosphate; potassiuim nitrosodisulfonate at 5℃;
Multi-step reaction with 3 steps
1: NaNO2, conc. HCl / H2O / 1 h / 0 °C
2: 1) 5N NaOH, Na2S2O4, 2) 12N H2SO4 / H2O / 2) 50 deg C
3: 12N H2SO4, 2N K2Cr2O7 / H2O / 0.05 h
Multi-step reaction with 2 steps
1: aqueous HCl; aqueous NaNO2
2: tin (II)-chloride; water; hydrochloric acid / und Behandeln der mit Hilfe von Schwefelwasserstoff von den Zinn-Salzen befreiten Reaktionsloesung mit Kaliumdichromat in wss.Schwefelsaeure
With [bis(acetoxy)iodo]benzene
With [bis(acetoxy)iodo]benzene In water; acetonitrile at 20℃; for 0.25h;
With bis-[(trifluoroacetoxy)iodo]benzene In water; acetonitrile at 0 - 20℃; for 1.5h;
Synthesis of Quinoline-5,8-dione (2).14
A sample of 8-quinolinol (1b, 0.145 g, 1.00 mmol) was treated with bis(trifluoroacetoxy)iodobenzene (PIFA, 0.946 g, 2.2 mmol). The 8-quinolinol was dissolved in a 2:1 ratio mixture of acetonitrile and water (3 mL total) and mixed with the PIFA, dissolved in an identical mixture. The 8-quinolinol was cooled to 0°C before being added dropwise to the PIFA in the reaction vessel (the mixture became a dark orange color). The reaction was carried out for 30 minutes at 0°C and then at room temperature for one hour under constant stirring. The extent of the reaction was monitored by thin layer chromatography (TLC, 250 μm). The desired quinoline-5,8-dione intermediate was formed and the acetonitrile solvent was evaporated under reduced pressure. The intermediate was dissolved in approximately 10 mL of water and extracted using five, 20 mL portions of dichloromethane (DCM). The orange-colored organic portions were collected and dried with anhydrous sodium sulfate (Na2SO4). The mixture was filtered and washed with DCM and the yellow filtrate was collected. TLC was run to confirm the presence of the intermediate and the DCM solvent was evaporated under reduced pressure to produce compound 2 (0.157 g, 99% crude yield). The remaining crude sample had a dark orange color and was used immediately after without further purification.
With [bis(acetoxy)iodo]benzene; In water; acetonitrile; at 0℃; for 1h;Inert atmosphere;
A solution of iodobenzene diacetate (10.35mmol, 3.3g) in 12mL CH3CN: H2O (2:1) was added to <strong>[578-67-6]quinolin-5-ol</strong> (3) (3.45mmol, 0.50g) at 0°C under N2 and stirred for 1h. After the reaction was completed, water (40mL) was added, and the solution was extracted with EtOAc (3×20mL). The organic phase was washed by brine and concentrated in vacuo to give 4 as a yellow solid, yield 82percent. MS (ESI) m/z = 160 [M+H]+.
General Method and Procedure for the Synthesis 6-(alkylthio- and alkylamino)- and bis-6,7-(alkylthio- and alkylamino)-substituted-5,8-quinolinequinones (Compounds 3 a-g and 3j-m).
General procedure: Method A (step-wise):The quinoline-5,8-dione (2, 0.050 g, 0.31 mmol) intermediate was dissolved in approximated 2 mL of methanol and treated with either a alkylthiol or alkylamino nucleophile in a 1:1 mmol ratio. The reaction was stirred at room temperature for one day, monitored through TLC, and stopped by evaporating the methanol under reduced presure. The resulting quinolinequinols intermediates were dark brown in color and weighed to determine the subsequent reaction molar quantities and used without further purification onto the next step.The quinolinequinols (reduced forms of 3 a-g and 3j-m) were oxidized using sodium periodate in a 1:1 mmol ratio. The crude mixtures were dissolved in DCM and methanol, in a 5:4 ratio, and the sodium periodate was dissolved in water. The milliliters of water were matched to the mmol quantity of the secondary intermediates used and the 1.25:1 DCM to methanol ratio used the portion of water as the baseline volume. The crude mixtures and reagents were mixed and the reactions ran for twenty minutes at room temperature while being stirred. The reactions were monitored through TLC using hexane:ethyl acetate (7:3) or (1:1) depending on the retention factor assigned, the organic layers (dark brown-colored) were collected using DCM and the reactions were stopped by drying over anhydrous sodium sulfate. The mother liquid containing the target compounds was decanted and the DCM/methanol solvent was evaporated under reduced pressure. The resulting dark brown solid samples were purified by the preparative TLC purification method.
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