| 50% |
With potassium permanganate; potassium hydroxide In water for 5h; Heating; |
3.1.1 Synthesis of 4, 5-diazafluoren-9-one
1,10-Phenanthroline (4.0g, 22.2mmol) and KOH (4.0g, 71.3mmol) in water (250mL) were boiled for 1h. A hot solution of KMnO4 (10.0g, 63.3mmol) in water (150mL) was added drop wise over ca. 2h to the boiling mixture. The reaction mixture was boiled for another 2h and was filtered hot. The orange filtrate was cooled and extracted with chloroform. The combined organic extract was dried over anhydrous Na2SO4 and the solvent was removed to obtain a crude product. Further purification by column chromatography on silica gel using acetone/ petroleum ether (2:1) as eluent yielded pure 4,5-diazafluoren-9-one as a yellow solid (2g, 50%). 1H NMR (CDCl3): δ=8.80 (d, 2H), 7.96 (d, 2H), 7.35 (d, 2H). |
| 48% |
With potassium permanganate; water; potassium hydroxide for 3h; Reflux; |
|
| 47.5% |
With potassium permanganate; potassium hydroxide In water for 9h; Reflux; |
1 Example 1 Synthesis of Compound 1
In a 5L three-necked flask,Add o-phenanthroline (36g, 0.2mol)And freshly prepared potassium hydroxide solution (2.5L, 0.35M),Stir and heat to reflux.Dissolve 105.2g of potassium permanganate in 400mLAfter the water is heated and dissolved,Add a constant pressure dropping funnel to the reaction mixture.Control the dripping speed,About 4h finished,The reaction was continued at reflux for 5 h.Hot filter,Wash cake,Get orange filtrate,Let stand to cool to room temperatureExtract with dichloromethane (3 x 20 mL),Combine the extracts,Dry with anhydrous Na2SO4,Spin-evaporated to a light yellow solid,Finally recrystallized from methanol,Vacuum dryingYellow needle crystals (Compound 1)(17.3 g, 0.095 mol), yield 47.5%. |
| 47.5% |
With potassium permanganate; potassium hydroxide In water for 5h; Reflux; |
1 Example 1 Synthesis of Compound 1
In a 5 L three-necked flask, phenanthroline (36 g, 0.2 mol) and a freshly prepared potassium hydroxide solution (2.5 L, 0.35 M) were added, stirred, and heated to reflux. 105.2 g of potassium permanganate was dissolved in 400 mL of water, dissolved by heating, and then added to the reaction mixture by a constant pressure dropping funnel to control the dropping rate. After about 4 hours, the reflux reaction was continued for 5 hours. The mixture was filtered while hot, and the filter cake was washed with water to give an orange-yellow filtrate, which was cooled to room temperature, and extracted with dichloromethane (3×20 mL). The extracts were combined, dried over anhydrous Na2SO4 and evaporated to give a pale yellow solid. Recrystallization of methanol, vacuum drying, to obtain yellow needle crystals (Compound 1)(17 · 3g, 0 · 095mol), yield 47 • 5% mp: 213°C. |
| 47.5% |
With potassium permanganate; potassium hydroxide In water for 9h; Reflux; |
1 Example 1: Synthesis of Compound 1
In a 5L three-necked flask,Add phenanthroline (36g, 0.2mol) and freshly prepared potassium hydroxide solution (2.5L,0.35 M), stirred and heated to reflux.Dissolve 105.2 g of potassium permanganate in 400 mL of water.After heating and dissolving,Adding to the reaction mixture using a constant pressure dropping funnel,Control the drop rate,After about 4 hours,The reflux reaction was continued for 5 h.Hot filtered,Wash the filter cake,Obtaining an orange filtrate,Allow to cool to room temperature,Extracted with dichloromethane (3 x 20 mL),Combine the extracts,Dry with anhydrous Na2SO4,Evaporated to give a pale yellow solid.Finally recrystallized from methanol,Vacuum drying,Yellow needle crystals (compound 1)(17.3 g, 0.095 mol), yield 47.5% |
| 45% |
With potassium permanganate; potassium hydroxide In water for 0.166667h; Reflux; |
|
| 43% |
With potassium permanganate; potassium hydroxide In water for 3h; Reflux; |
|
| 41% |
With potassium hydroxide; potassium permanganate In water at 80℃; for 0.5h; |
7
A 2 L separable flask was charged with 18 g (99.9 mmol) of fenanthroline, 18 g (320.8 mmol) of potassium hydroxide and 900 g of water, and the content was heated to 80° C. A mixed liquid comprising 45 g of potassium permanganate and 720 g of water was dropwise added to the content while the content was stirred at that temperature. After the completion of addition, the stirring was further continued for 30 minutes and the reaction was terminated. The hot reaction liquid was filtered to remove manganese dioxide. Then the reaction liquid was allowed to cool to room temperature, and then extracted with chloroform. The extract was treated in the conventional manner, and concentrated to give a yellow powder. Recrystallization of the powder from acetone gave 7.54 g of a yellow needle crystal (yield: 41%). The identification of the crystalline compound was conducted by 1H-NMR and 13C-NMR. 1H-NMR: (CDCl3, ppm); 8.80 (d, J=5.2, 2H), 8.05 (dd, J=7.6, 1.6, 2H), 7.36 (dd, J=7.6, 5.2, 2H) 13C-NMR: (CDCl3, ppm); 189.42, 163.31, 155.10, 131.45, 129.30, 124.69 |
| 39.3% |
With potassium permanganate; potassium hydroxide at 125℃; for 13h; |
1 Synthesis of Compound 1 of Example 1
In a 5-L three-necked flask, 1,10-phenanthroline (50 g, 0.28 mol) was added.2000mL new potassium hydroxide solution (0.36mol/L),The mixture was heated and dissolved with stirring, and 131.1 g of potassium permanganate (KMnO4) was weighed to form a saturated solution.The reaction warmed to 125°C.The saturated KMnO4 saturated solution was dropped into the reaction with a constant pressure dropping funnel, and was dripped for about 1 hour.Continue to react for more than 12h.After the end of the reaction, using a Buchner funnel hot filtration, cooling, and then extracted with dichloromethane (CH2Cl2, 3 x 20mL), the filtrate was dried over anhydrous sodium sulfate, rotary steam,Obtained pale yellow solid product 5H-cyclopenta[1,2-b:5,4-b']dipyridin-5-one (Compound 1) (20.8 g, 0.11 mol) in a yield of 39.3% |
| 38% |
With potassium permanganate |
|
| 35.5% |
With potassium permanganate; potassium hydroxide In water for 2h; |
1.4 Preparation of 4,5-diazofluoren-9-one
A mixture of 2. 5 g (13.75 mmol) of 1,10-phenanthroline,2. 5 g (44.65 mmol) of K0H was dissolved in 250 ml of water and heated to boiling.Another weighing 6.25 (39.5mmol) KMn04 dissolved in 200ml of hot water,The KMn04 solution was slowly added dropwise to the above-mentioned phenanthroline reaction solution,Control 2h drops finished,After dripping the reaction solution to continue boiling lOmin,Filter hot to remove Mn02,The filtrate was extracted with chloroform (3X200 ml)The organic phase was dried with anhydrous MnS04,The solvent was removed by distillation under reduced pressure on a rotary evaporator,The resulting solid was recrystallized from acetone to give a yellow crystal, 75 g,The yield was 35. 5% |
| 25% |
With potassium hydroxide; potassium permanganate In water Heating; |
|
| 25% |
With potassium permanganate; potassium hydroxide In water for 2h; Reflux; |
1.a (A) synthesis of formula (1) 4,5-dinitrogenfluoren-9-one
Constant voltage dropping funnel in a 500 ml three-mouth bottle, sequentially adding a 1,10-O-phenan throline 5.9g in other words 0.03mol, potassium hydroxide 3.06g in other words 0.055mol, distilled water 200 ml, electromagnetic stirring under heating to reflux, the solid completely dissolved after to, self-constant-voltage dropping funnel dropping slowly added in an aqueous solution of potassium permanganate, the aqueous solution of potassium permanganate 15.2g potassium permanganate dissolved in 125 ml distilled water, after the add, to continue to reflux reaction 2h, hot filtering, cooling the filtrate after precipitation with yellow acicular crystal, pulls out worry, washing, drying to obtain light yellow crystal, yield 25%, |
| 25% |
With potassium permanganate; potassium hydroxide In water for 3h; Heating; |
|
| 23.02% |
With potassium permanganate; potassium hydroxide In water for 0.5h; Reflux; |
2.3.5. 4,5-Diazafluorene-9-one (L5)
1,10-Phenanthroline (0.025 mmol) and KOH (0.046 mmol) were added to 200 mL water and a resulting mixture was brought to a reflux followed by dropwise addition of aqueous solution of potassium permanganate (0.08 mmol) to it. After addition, the solution was refluxed for 30 min and filtered off to remove MnO2. When thesolution was cooled, crude 4,5-diazafluoren-9-one precipitated as yellow needles. Crystallization from water gives a desired ketone in pure form. Yield: 23.02%, m.p.: 212-213 °C, chemical formula (mol.wt.): C11H6N2O (182.18 g/mol), elemental analysis: calc. (%): C, 72.52; H, 3.32; N, 15.38, found (%): C, 72.49; H, 3.34; N, 15.35. 1H NMR (CDCl3, 400 MHz) δ/ppm: 8.828, (dd, 2H, H3,6); 8.020, (dd, 2H, H1,8); 7.381, (dd, 2H, H2,7), 13C NMR (CDCl3, 100 MHz) δ/ppm: 188.42, (C9); 155.11, (C11,13); 152.38, (C3,6); 131.69, (C10,12); 129.40, (C1,8); 124.84, (C2,7), FT-IR (KBr, 4000-626 cm-1): ν(C-H), 3032; ν(C=O), 1713, ν(C=C), 1535; ν(C=N), 1497; ν(C=H), 710 (s). |
| 23.5% |
With potassium permanganate; potassium hydroxide In water at 70 - 80℃; |
1.1 (1) Synthesis of Compound 1
Weigh 5.00 g (25.3 mmol) of phenanthroline monohydrate and 5.00 g (89.3 mmol)Potassium hydroxide in water, heated to boiling,13.00 g (82.3 mmol) of potassium permanganate in hot water (150 mL water, stirring)70 ~ 80 °C) drip. After the addition was completed, the mixture was further stirred for 10 minutes while boiling, and filtered while hot.The solution was orange-red, and after cooling, it was extracted three times with chloroform, and the organic phases were combined and dried over anhydrous magnesium sulfate.Filter and finally distill off the solvent under reduced pressure. The acetone is recrystallized to give a pale yellow needle crystal product.The yield was 23.5% (1.08 g). |
| 21% |
With potassium hydroxide; potassium permanganate In water for 1h; Heating; |
|
|
With potassium permanganate |
I EXAMPLE I
All synthetic preparations were performed under ambient oxygen conditions. All reagents were used as purchased without further purification. 4,5-Diaza-9-fluorenone was synthesized by the oxidation of 1,10-phenathroline with KMnO4 according to literature procedures, as described, for example, by L. J. Henderson, J.; Fronczek, F. R.; and Cherry, W. R., in J. Am. Chem. Soc. 1984, 106, 5876-5879. 4,5-diaza-9-fluorenone hydrazone was prepared by refluxing a mixture of the fluorenone and hydrazine hydrate in methanolic solution with a catalytic amount of acetic acid to prevent azine formation, as described, for example, by Mlochowski, J.; and Szulc, Z. in Polish J. Chem. 1983, 57, 33-39. |
|
With potassium hydroxide; potassium permanganate In water at 90 - 95℃; for 0.5h; |
1.1
(1) Synthesis of 4,5-diazafluorenone (intermediate compound 1); 3.4 kg (21.5 mol) of potassium permanganate and 54.7 kg of water were stirred at 30° C. overnight, to form an aqueous solution. Next, 1.3 kg (6.57 mol) of 1,10-phenanthroline monohydrate, 102.6 kg of water, and 1.36 kg of potassium hydroxide were stirred under heat at 90° C. Then, the aqueous potassium permanganate solution prepared in advance was added dropwise in the resultant at a temperature in the range of 90° C. or higher to 94° C. or lower. After the completion of the dropwise addition, the resultant was stirred at 95° C. for 30 minutes, and then cooled to a temperature in the range of 40° C. or higher to 50° C. or lower. 15 L of warm water was added to the resultant, and the mixture was subjected to celite filtration. Then, 16.5 kg of methylene chloride was added to the filtrate, and then extracted. The aqueous layer was extracted twice with 16.5 kg of methylene chloride, and the organic layer was concentrated after mirabilite desiccation. Crude crystals were washed with 3 L acetone to remove slurry, thereby obtaining 550 g of 4,5-diazafruorenone (intermediate compound 1). |
|
With potassium hydroxide; potassium permanganate; water |
|
|
With potassium hydroxide; potassium permanganate |
|
|
With potassium permanganate In water Reflux; |
|
|
Stage #1: 1,10-Phenanthroline With potassium hydroxide In water Reflux;
Stage #2: With potassium permanganate In water |
|
|
With potassium permanganate; potassium hydroxide |
|
|
With potassium permanganate; potassium hydroxide In water Reflux; |
|
|
With potassium permanganate; potassium hydroxide In water Reflux; |
|
|
With potassium permanganate; potassium hydroxide |
|
|
With potassium permanganate; potassium hydroxide |
|
|
With potassium permanganate; potassium hydroxide In water for 1h; Reflux; |
|
|
With potassium permanganate; potassium hydroxide Reflux; |
|
|
With potassium permanganate; potassium hydroxide at 100℃; |
|
| 71.6 mg |
With potassium permanganate; potassium hydroxide In water at 100℃; for 3.5h; |
1.4 4) Preparation of intermediate a
It is prepared by using 1,10-phenanthroline monohydrate as a raw material in an aqueous solution of potassium permanganate and potassium hydroxide. 1,10-phenanthroline monohydrate (5 g, 25.22 mmol) and potassium hydroxide (2.8 g, 49.91 mmol) were dissolved in 200 mL of distilled water and heated to 100 ° C under elevated temperature. Potassium permanganate (12.8 g, 80.99 mmol) was dissolved in 200 mL of distilled water, dissolved by heating, and slowly added dropwise to the above mixture over 1 hour, and the reaction was continued at 100 ° C for 2.5 h, and filtered while hot. After the filtrate was cooled, the pH was adjusted to 8-9 with 10% hydrochloric acid and then extracted with dichloromethane (3×200mL), dried over anhydrous sodium sulfate and filtered. Concentrated organic phase,Silica gel column chromatography (dichloromethane as mobile phase)Purification to give a yellow-white solid a; |
|
With potassium permanganate; potassium hydroxide In water at 100℃; |
|
|
With potassium permanganate; potassium hydroxide In water Heating; |
|
|
With potassium permanganate; water; potassium hydroxide at 100℃; for 5h; |
|
|
Stage #1: 1,10-Phenanthroline With potassium hydroxide In water at 100℃; for 0.5h;
Stage #2: With potassium permanganate In water for 5h; Reflux; |
2.2.2 Synthesis of 4, 5-diazafluoren-9-one (DAFO)
DAFO was synthesized according to a published procedure[28] with minor modification. In a typical process, 3 g of1, 10-phenanthroline and 2.5 g of KOH were dissolved in100 mL deionized water in a flask. The mixture was stirredand refluxed at 100 °C for 30 min. Then 6.8 g KMnO4wasdissolved in 84 mL boiling deionized water. The solutionwas added dropwise into the flask within 30 min, and reactedfor 5 h under reflux and stirring. After the reaction, the mixturewas hot-filtered. The filtrate was cooled overnight tocrystallize, then light yellow crystals precipitated out. Thesolid was recrystallized with water followed by drying at70 °C under vacuum overnight. The DAFO was obtainedwith a yield of about 20.9%. The NMR results are shownin the Figure S1 and Figure S2. 1H-NMR (CDCl3, ppm):δ = 7.36 (dd, 2 H), 8.01 (dd, 2 H), and 8.81 (dd, 2 H), 13CNMR(CDCl3, ppm): δ = 125.07, 129.63, 131.84, 155.52,163.69, 189.89. |
|
With potassium permanganate; potassium hydroxide Reflux; |
|
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
