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CAS No. : | 571-60-8 | MDL No. : | MFCD00003977 |
Formula : | C10H8O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PCILLCXFKWDRMK-UHFFFAOYSA-N |
M.W : | 160.17 | Pubchem ID : | 11305 |
Synonyms : |
|
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P264-P270-P280-P301+P312+P330-P302+P352+P332+P313+P362+P364-P305+P351+P338+P310-P501 | UN#: | 1759 |
Hazard Statements: | H302-H315-H318 | Packing Group: | Ⅲ |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; dimethyl sulfate; In water; acetone; | A. 5,8-Dimethoxy-2-tetralone To one liter of acetone were added 50.0 g (0.31 mol) of 1,4-dihydroxynaphthalene. To the resulting solution then were added 95.0 g (0.69 mol) of powdered potassium carbonate and 65 ml (0.69 mol) of dimethyl sulfate. The resulting mixture was stirred at reflux for 18 hours after which it was diluted with two liters of water and then extracted with methylene chloride. The organic extracts were combined,.dried over sodium sulfate, and evaporated in vacuo to give a black oil. The oil was distilled in vacuo to give 12.5 g of 1,4-dimethoxynaphthalene as an orange crystalline solid. b.p. 155 C. at 5 mm Hg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 2,2'-bipyridylchromium peroxide In benzene for 0.5h; Heating; | |
100% | With dihydrogen peroxide In benzene at 50℃; for 1.5h; | |
100% | With 2,2'-bipyridylchromium peroxide In benzene for 0.5h; Heating; effect of various chromium(VI) based oxidants; |
100% | With periodate Ultra resin In methanol; dichloromethane at 20℃; for 0.33h; | |
100% | With μ-oxo-[bis(trifluoroacetoxy)iodo]benzene In lithium hydroxide monohydrate; acetonitrile at 0℃; for 2h; | |
99% | With oxygen In chloroform; lithium hydroxide monohydrate at 20℃; for 2h; | |
99% | With [(4,5-dihydro-4,4-dimethyl-2-phenyloxazole)Ru(CH3CN)4]PF6; dihydrogen peroxide In tetrahydrofuran; lithium hydroxide monohydrate at 0 - 20℃; for 0.0833333h; | 10 General procedure for 2a catalyzed H2O2 oxidation of dihydroxy arenes General procedure: To a solution of dihydroxy arene (0.34 mmol) and 2a (1.98 mg,0.0034 mmol) in THF (1.0 mL) was added H2O2 (30% aq, 50.0 mL,0.44 mmol) at 0 C. After 5 min the starting material had completelyoxidized to the quinone product. The quinone product wasthen extracted by ether or dichloromethane, dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford thedesired product. Pleasingly, the resulted quinone products werepure enough and there is no necessity for column chromatographyin most of the cases. |
99% | With Au/C; potassium carbonate In chloroform; lithium hydroxide monohydrate at 20℃; for 24h; | |
98% | With sodium (meta)periodate In chloroform; lithium hydroxide monohydrate Ambient temperature; | |
98% | With sodium (meta)periodate In chloroform; lithium hydroxide monohydrate Ambient temperature; other oxidants, other solvents, without catalyst, various reaction times; | |
98% | With K10 montmorillonite; iodic acid for 0.00833333h; microvawe irradiation; | |
98% | With carbon nanotube-rhodium nanohybrid; air In chloroform; lithium hydroxide monohydrate at 20℃; for 5h; | |
98% | With sulfuric acid; sodium bromide In dichloromethane; lithium hydroxide monohydrate at 15℃; for 2.98h; Electrolysis; | General procedurefor oxidation of 1,4-dihydroxybenzene General procedure: To a stirred solution of 1,4-dihydroxybenzene 1.1 g (10 mmol) in 25 ml of CH2Cl2 taken in a jacketed glass reactor (Fig. 1), a 12.5% aqueous NaBr solution (45 ml) acidified with H2SO4 (2.75 g) was added and the resulting biphasic solution was cooled to 15 °C. Two smooth platinum foil electrodes (3x2 cm2) were placed 1 cm apart in the upper aqueous phase and electrolysed galvanostatically at a current density of 30 mA/cm2 for 2.98 h (Fig. 2). The reaction was monitored by HPLC (Shimadzu). The voltage observed during electrolysis is 2.1 V. After completion of the reaction (2 F/mol), the lower organic phase containing the quinone or brominated product was isolated by simple phase separation. The aqueous portion was extracted once with 25 ml CH2Cl2. The combined organic phase was washed with brine (2x25 ml), dried with anhydrous Na2SO4 and concentrated in vacuo to isolate the solid product 1,4-benzoquinone (1.06 g,99% yield). The crude product was boiled with 20 ml of n-hexane and the resulting yellowish clear solution was transferred to a conical flask. On cooling to room temperature, separated yellow needles were filtered and then characterised by its melting point, HPLC, IR, and NMR spectra. The isolated yield of the product and current efficiency were determined. |
98% | With oxygen; mesoporous silica In dichloromethane at 25℃; for 0.42h; | 3.3. General Procedure for P1/Silica-gel Combined Catalyst Catalyzed Aerobic Oxidation of Various Dihydroxy Arenes General procedure: In a two-neck 100 ml round bottomed flask connected tomolecular oxygen balloon (1.0 atm) and containing dihydroxyarene (0.1 mmol), P1 (100 mg, 0.1 mmol/g loading)and 250 mg silica-gel, a 3.0 mL of CH2Cl2 was injected and the reaction mixture was stirred at room temperature and followed by TLC until the starting material had completely converted to quinone. The quinone product was extracted with CH2Cl2 or ether and was obtained under reduced pressure.The further purification of most of the quinone product was not necessary. The P1/silica-gel combined catalyst was washed several times with ether or CH2Cl2 until it became completely clean and dried under vacuum to be ready for the next cycle. |
98% | With oxygen; mesoporous silica In dichloromethane at 25℃; for 0.42h; | 3.3. General Procedure for P1/Silica-gel Combined Catalyst Catalyzed Aerobic Oxidation of Various Dihydroxy Arenes General procedure: In a two-neck 100 ml round bottomed flask connected tomolecular oxygen balloon (1.0 atm) and containing dihydroxyarene (0.1 mmol), P1 (100 mg, 0.1 mmol/g loading)and 250 mg silica-gel, a 3.0 mL of CH2Cl2 was injected and the reaction mixture was stirred at room temperature and followed by TLC until the starting material had completely converted to quinone. The quinone product was extracted with CH2Cl2 or ether and was obtained under reduced pressure.The further purification of most of the quinone product was not necessary. The P1/silica-gel combined catalyst was washed several times with ether or CH2Cl2 until it became completely clean and dried under vacuum to be ready for the next cycle. |
97% | With air; copper(II) sulphate In various solvent(s) at 100℃; for 8h; | |
97% | With lithium hydroxide monohydrate; oxygen In chloroform at 20℃; for 3h; | |
96% | With zirconium phosphate; air; phthalocyanine[Fe(3+)] In 1,4-dioxane; lithium hydroxide monohydrate at 20℃; for 1h; | |
96% | With trifluorormethanesulfonic acid; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In 1,4-dioxane at 20℃; for 0.0833333h; | General Procedure for the IBX-TfOH mediated oxidation of alcohols General procedure: To the suspension of IBX (1.1 equiv., or 1.1 mmol) and TfOH (2-5 mol %, or 0.02-0.05 mmol) in 3 mL 1,4-dioxane, alcohol (1.0 equiv., 1.0 mmol in 2 mL 1,4-dioxane) was added at room temperature, and the reaction mixture was vigorously stirred till the complete consumption of alcohol, as indicated by TLC. The solvent was evaporated under reduced pressure, and the resulting residue was diluted with 10 mL of dichloromethane. The heterogeneous mixture was stirred for 5 minutes and filtered. The residue was washed with dichloromethane (3×3 mL) and the filtrate was evaporated to dryness to obtain the desired product in sufficiently pure form. |
95% | With CAN In solid for 2h; ultrasonic irradiation; | |
95% | With polymeric complex of oxodiperoxochromium(VI) compound and pyrazine (Pyz-CrO5)n In dichloromethane for 0.2h; Ambient temperature; | |
95% | With tert.-butylhydroperoxide; palladium(II) benzoate In lithium hydroxide monohydrate; isopropanol; propan-2-one at 20℃; for 48h; | |
94% | With oxygen; 5,10,15,20-tetraphenyl-21H,23H-porphine In dichloromethane-d2 at -20℃; for 1.5h; Irradiation; | |
92% | With benzeneseleninic anhydride In tetrahydrofuran Ambient temperature; | |
92% | With thionyl chloride In benzene for 2h; Heating; | |
90% | With tetrabutylammonium hexanitratocerate(IV) In dichloromethane for 0.0833333h; Ambient temperature; | |
89% | With 4-phenoxyphenyl telluric anhydride In glacial acetic acid for 0.666667h; Ambient temperature; | |
89% | With dibenzoyl peroxide In dichloromethane; isopropanol for 5h; | |
87% | With pyridine; p-anisylmorpholinotellurium(IV) dichloride In dichloromethane for 0.166667h; Ambient temperature; | |
84% | With ruthenium(III) trichloride hydrate; oxygen; C25H44NO2PS In 1,2-dichloro-ethane at 23℃; for 40h; | |
82% | With pyridine; tert.-butylhydroperoxide; iron(III) chloride at 20℃; for 0.166667h; | |
79% | With sodium perborate In glacial acetic acid at 50 - 60℃; for 4h; | |
78% | With silver(II) oxide; HNO3 In propan-2-one at 20℃; | |
75% | With sodium dihydrosulfite In diethyl ether; lithium hydroxide monohydrate | |
74% | With dihydrogen peroxide; glacial acetic acid In lithium hydroxide monohydrate at 80℃; for 8h; | |
70% | With sodium chlorine monoxide In chloroform for 0.25h; Ambient temperature; | |
68% | With tert.-butylhydroperoxide In benzene at 70℃; for 48h; Var.: without cat.; | |
66% | With 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In acetonitrile for 3h; Ambient temperature; | |
65% | With ammonium peroxydisulfate; mesoporous silica for 0.05h; | |
60% | With tert.-butylhydroperoxide In benzene at 70℃; for 48h; | |
2.7% | In propan-2-one | 17 EXAMPLE 17 EXAMPLE 17 The reaction was made under the same conditions as those in the procedure of EXAMPLE 1 except that the aromatic diol compound was 80g (0.5 mole) of 1,4-naphthalenediol and 500 ml of acetone was used as the solvent. Ureacted 1,4-naphthalenediol was present at 2.7% and the yield of 1,4-naphthoquinone was 97.0%. |
With sodium chlorate; sulfuric acid; vanadium pentoxide unter Kuehlung; | ||
With potassium nitrosodisulfonate | ||
With oxygen In lithium hydroxide monohydrate at 30℃; | ||
durch Oxydationsmittel; | ||
With oxygen In lithium hydroxide monohydrate at 30℃; | ||
With oxygen In methanol; phosphate buffer at 37℃; | ||
97 %Chromat. | With dihydrogen peroxide; silver(I) oxide In methanol; lithium hydroxide monohydrate at 25℃; for 0.5h; chemoselective reaction; | |
> 99 %Chromat. | With pyridine; tert.-butylhydroperoxide; nickel cobalt oxide In lithium hydroxide monohydrate; acetonitrile at 20℃; for 0.5h; | |
With [bis(acetoxy)iodo]benzene In toluene | ||
With air | ||
With pyridine; tert.-butylhydroperoxide In acetonitrile at 80℃; for 1h; | 2 General procedure for the oxidation of benzylic methylenes General procedure: A mixture of 4,4-diuorodiphenylmethane (178.4 L,1.0 mmol) and P4VPDVB2.5-40%-Fe(III) catalyst (2.0 mol%), pyridine (8.0 L,0.1 mmol), TBHP (5.0-6.0 M in decane, 545.0 L, 3.0 mmol) and 1.0 mL acetonitrile was dissolved in a 25 mL single-necked flask fitted with a reflux condenser. The mixture was heated at 80°C for 24 h under air atmosphere in an oil bath. Then the mixture was cooled to 25°C and centrifuged to get a catalyst and supernatant solution. Then the solution was analyzed by Agilent 7890/5975C-GC/MSD using nitrobenzene as an internal standard. A calibration curve for each reactant and product has been built, which is included in the ESI†. The in situ 1H NMR monitoring of the reaction conversion and yield was performed in the DMSO-d6 solvent, the crude sample of entry 11 in Table 3 was filtered for direct 1H NMR analysis (see ESI†). Furthermore, the products of entries 1 and 7 in Table 2 were isolated through column chromatography and the isolated yields were provided. | |
With Pt(5%)Bi(5%)/C; dihydrogen peroxide In methanol; lithium hydroxide monohydrate at 60℃; for 0.666667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,4-dioxane at 60 - 65℃; Behandeln des Reaktionsprodukts mit Ag2O in Aether; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With pyridine at 20℃; for 1h; | |
83% | With pyridine at 20℃; for 5h; | 1,4-di-O-acylonaphtalene SI-6 General procedure: A round-bottom flask was charged with 1,4-naphtoquinone (7.25 g, 45.84 mmol), which was dissolvedin AcOEt (150 mL). The flask was capped with a rubber septum and the Ar atmosphere wasestablished. The septum was removed, 10% Pd/C (0.17 g) was added and the flask was againcapped with a septum. The reaction mixture was flushed with H2 and was then stirred at roomtemperature under H2 atmosphere for 18 hrs. After completion of the reaction, Pd/C was filtered off,and the reaction mixture was filtered through silica pad with AcOEt. Concentration in vacuo afforded6.98 g (98% crude) 1,4-dihydroxynaphtalene as a brown solid which was used in the next step withoutfurther purification.1,4-dihydroxynaphtalene (6.97 g, 43.55 mmol) was dissolved in pyridine (69.95 mL) and aceticanhydride (62.57 mL) was added. The reaction was carried at room temperature for 5 hrs and thenthe reaction mixture was evaporated to dryness. Purification by column chromatography(Hexane:AcOEt = 3:1) afforded 9.33 g of 1,4-di-O-acylonaphtalene SI-6 as white powder (83% aftertwo steps). |
54% | In pyridine at 20℃; for 1h; | 1 ,4-Naphthalenediol (Ig, 6.25mmol), pyridine (10ml) and acetic anhydride (10ml) was stirred at room temperature for 1 hour. The reaction mixture was poured into a separating funnel with distilled water (100ml), brine (10ml) extracted three times with chloroform (60ml). The organic layer was isolated, dried with sodium sulphate and evaporated under reduced pressure. The crude product obtained was purified by column chromatography using silica gel as adsorbent and chloroform as eluent. 1,4-Diacetoxynaphthalene (0.83g, 54%) was removed as a white solid.1H NMR (d-CDCh) δ 2.45 (6H, s, 2 CH3), 7.26 (2H, s, 2 CH), 7.54 - 7.57 (2H, m, 2 CH),7.90 - 7.88 (2H, m, 2 CH).13C NMR (d6-CDCl3) 5 20.89, 117.57, 121.51, 126.89, 127.52, 144.22, 169.27MS-ESI mlz 262.10 [M + NH4J+CHN: Found (C=68.86%, 4.77%), Theoretical (C=68.85%, 4.95%) |
With zinc(II) chloride | ||
With sodium acetate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; acetone | ||
With potassium carbonate In acetone Heating / reflux; | To a 250 mL round bottom flask, 2.68 g (16.7 mmol) of 1,4-dihydroxynapthalene, 2.9 mL (33.5 mmol) of allyl bromide, 4.61 g (33.5 mmol) of potassium carbonate, and 15.0 mL (133.9 mmol) of dry acetone were added. The solution was set to reflux overnight under a drying tube. It was next vacuum filtered to remove the potassium carbonate. An extraction was then performed on the filtrate with ethyl ether (100 mL), and the ether layer was collected. The ether layer was washed twice with 50 mL of 1 M sodium hydroxide to remove any phenolic excess. It was next washed twice with 25 mL of purified water, and the ether layer was collected. The ether layer was dried over sodium sulfate, and then it was vacuum filtered to remove the sodium sulfate. A brown oily residue remained in the bottom of the flask. Silica gel column chromatography was performed on the residue to obtain the pure product. The residue was dissolved in chloroform. The column was made of chloroform. The product was placed on the rotary evaporator and the solvent was removed. Thin Layer Chromatography was performed on the final product as an viscous clear oil. The chamber was filled with chloroform. The product had an Rf value of 0.78.To a 50 mL round bottom flask containing the diallyl 1,4-dihydroxynapthalene ether was added 13 mL of dodecane. The system was degassed with N2 for five minutes. The solution was refluxed at 220° C. for 21/4 hours. The solution was stirred overnight at which time a solid had formed. The solid was isolated by vacuum filtration and the residue was washed with hexanes. 2,3-diallyl 1,4-dihydroxynapthalene was isolated as a fine, tan power (3.08 g, 77% yield). It was found to have a melting point between 132-138° C. | |
With potassium carbonate; acetone |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.31 g | Naphthoquinone (2 g, 12.6 mmol) was dissolved in 50 ml of THF, palladium on carbon was added, and the reaction was carried out under hydrogen atmosphere for 12 h.The solution was filtered and the filtrate was added with sodium hydride under nitrogen. After stirring at 0 C for 10 min, dimethyl sulfate was slowly added dropwise and the reaction was continued for 4 h. THF was spin-dried, extracted with ethyl acetate, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 1,4-dimethoxynaphthalene (1.31 g). The resulting 1,4-dimethoxynaphthalene (1 eq) was dissolved in 5 ml of methylene chloride, and tin tetrachloride (1.2 eq) was slowly added dropwise thereto under ice-cooling. After stirring for 10 min,1,1-dichloromethyl ether (1.2 eq) was added dropwise,The reaction was carried out at 0 C for 3 h.To the reaction solution was added ice water, extracted with DCM, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 1,4-dimethoxy-2-naphthaldehyde.NaH was added to a 50 ml flask, under nitrogen, 5 ml of toluene and triethyl 2-phosphonopropyl ester were added and the reaction was heated to 110 C for 30 min. 1,4-dimethoxy-2-naphthaldehyde dissolved in 2ml of toluene, slowly dropwise to the reaction solution, continue to reflux 12h. Acidified with 2 M HC1, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Column chromatography gave Intermediate 18-2. Intermediate 18-2 was dissolved in ethanol, potassium hydroxide was added and the reaction was allowed to react for 1 h at reflux. The solvent was dried under reduced pressure to give intermediate 18-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With glacial acetic acid; zinc powder Ambient temperature; sonication, less than 5 min; | |
100% | With hydrogen for 6h; | 5 A mixture of 1,4-naphthoquinone (40,0 g, 0.253 mol) and 10% Pd/C (0.4 g) was shaken under H2 (50 psig) for six hours. The catalyst was removed by filtration, and the filter pad was washed with degassed MeOH (2 x 25 mL). The filtrate was spin-evaporated in vacuo to a solid, then further dried using a mechanical pump to give 40.5 g (100%) of product suitable for further transformation |
100% | With sodium dihydrosulfite In diethyl ether; water monomer at 20℃; for 1h; |
98% | With glacial acetic acid; zinc powder ultrasound; | |
97.3% | With sodium dihydrosulfite In diethyl ether for 0.5h; | |
93% | With isopropanol; zirconium oxide for 2h; Heating; | |
93% | With sodium dihydrosulfite; water monomer In diethyl ether for 0.5h; Inert atmosphere; | |
92% | With hydrogen In benzene for 1h; | |
88% | With boron trifluoride diethyl ether complex; sodium iodide In acetonitrile 1.) 0 deg C, 10 min, 2.) room temperature, 20 min; | |
85% | With aluminum triiodide In acetonitrile for 1h; Heating; | |
81% | With anhydrous zinc chloride; zinc powder In ethanol for 1.5h; Heating; | |
80% | With 1,1,3,3-Tetramethyldisiloxane; iodine In dichloromethane for 0.5h; Heating; | |
80% | With 1,1,3,3-Tetramethyldisiloxane; iodine In dichloromethane for 0.5h; Heating; | |
74% | With sodium dihydrosulfite In solid | |
74% | With glacial acetic acid; zinc powder at 0 - 20℃; for 17h; Inert atmosphere; | |
70% | With Caswell No. 744A In water monomer; acetone at 20℃; | |
In n-heptane at 19.9℃; Irradiation; other solvent: ethanol; | ||
Irradiation; half life; | ||
With sodium dihydrosulfite; water monomer zuletzt bei Siedetemperatur; | ||
With phenylhydrazine | ||
durch Einw. von untergaeriger Hefe; | ||
With hydrogenchloride at 40 - 50℃; Electrolysis; | ||
With black phosphorus; hydrogen iodide | ||
With hydrogenchloride; tin | ||
With hydrogenchloride; stannous chloride | ||
With Phenyl azide | ||
With with thiophene dactivated nickel-copper catalysts; toluene at 180℃; Hydrogenation; | ||
In n-heptane at 293℃; Irradiation; other solvent: ethanol; | ||
With sodium meta-bisulphite In water monomer for 2h; | ||
With sodium dihydrosulfite In dichloromethane; water monomer for 0.0833333h; Ambient temperature; | ||
With chloro-trimethyl-silane; 1,1,3,3-Tetramethyldisiloxane; sodium iodide 1.) chlorotrimethylsilane, sodium iodide, acetonitrile, 5 min; 2.) 1,1,3,3-tetramethyldisiloxane, dichloromethane, reflux, 30 min; Yield given. Multistep reaction; | ||
With hydrogen In ethanol | ||
With hydrogen In methanol | ||
With sodium dihydrosulfite In diethyl ether for 0.166667h; | ||
With hydrogenchloride; Caswell No. 744A In methanol at 0℃; for 0.166667h; | ||
With hydrogen In acetone at 20℃; for 24h; | ||
With sodium tetrahydridoborate In ethanol; water monomer for 0.5h; | ||
With sodium dihydrosulfite In diethyl ether; water monomer at 20℃; for 1h; | ||
With hydrogen In tetrahydrofuran at 20℃; for 2h; | ||
Multi-step reaction with 2 steps 1: benzene / 60 °C 2: hexamethylphosphoric acid triamide / 60 °C | ||
Multi-step reaction with 2 steps 1: zinc-powder; triethylamine / 25 °C 2: ethanol; aqueous NaOH / Kochen des Reaktionsgemisches mit konz. wss. HCl und SnCl2 | ||
With stannous chloride In hydrogenchloride; ethanol | R.41 1,4-Naphthohydroquinone Reference Example 41 1,4-Naphthohydroquinone To 1,4-naphthoquinone (25 g) suspended in ethanol (100 ml) was added a solution (150 ml) of stannous chloride (368 g) in concentrated hydrochloric acid gradually at room temperature. After the evolution of heat had ceased and a homogeneous state was established, the reaction mixture was brought back to room temperature and the resulting crystals were collected by filtration, rinsed with water, and dried to provide the title compound (18.2 g). m.p. 210°-213° C. | |
With sodium dihydrosulfite; Etamon In tetrahydrofuran; water monomer at 20℃; for 0.333333h; | ||
With palladium 10% on activated carbon; hydrogen In tetrahydrofuran at 20℃; for 4.16667h; Inert atmosphere; | ||
With sodium dihydrosulfite In diethyl ether; water monomer at 30℃; for 1h; Inert atmosphere; | ||
With sodium dihydrosulfite; water monomer In diethyl ether; ethyl acetate at 25℃; for 0.5h; | ||
With bis(η4-1,5-cyclooctadiene)-di-μ-methoxy-diiridium(I); 4,4,5,5-tetramethyl-1,3,2-dioxaborolane; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 4h; | General hydroborylation-bromination procedure General procedure: To [Ir(COD)OMe]2 (7.3 mg, 11 μmol) and 4,4'-di-tert-butyl-2,2'-bipyridine (7.0 mg, 26 μmol) in a flame-dried vial under nitrogen were added THF (0.7 mL), pinacolborane (0.18 mL, 1.24 mmol) and 1,4-dimethoxynaphthalene (7) (188 mg, 1.0 mmol). The mixture was stirred at 80 °C for 24 h then filtered through Celite and concentrated in vacuo to afford crude pinacol ester 13 (100% conversion by 1H NMR) that was used directly in the next step. | |
With sodium dihydrosulfite; L-ascorbic acid In methanol at 20℃; for 5h; Inert atmosphere; Darkness; | ||
With hydrogenchloride; dichloro-λ2-stannane dihydrate In methanol; water monomer for 3h; Reflux; | ||
With hydrogen; platinum In [(2)H6]acetone; water monomer for 0.166667h; Inert atmosphere; | ||
Multi-step reaction with 2 steps 1: pyridine-4-carbonitrile / n-Pentane / 12 h / 50 °C / Inert atmosphere; Sealed tube 2: water monomer / 0.17 h / 20 °C / Inert atmosphere | ||
With palladium on activated charcoal; hydrogen In tetrahydrofuran for 12h; | Naphthoquinone (2 g, 12.6 mmol) was dissolved in 50 ml of THF, palladium on carbon was added, and the reaction was carried out under hydrogen atmosphere for 12 h.The solution was filtered and the filtrate was added with sodium hydride under nitrogen. After stirring at 0 ° C for 10 min, dimethyl sulfate was slowly added dropwise and the reaction was continued for 4 h. THF was spin-dried, extracted with ethyl acetate, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 1,4-dimethoxynaphthalene (1.31 g). The resulting 1,4-dimethoxynaphthalene (1 eq) was dissolved in 5 ml of methylene chloride, and tin tetrachloride (1.2 eq) was slowly added dropwise thereto under ice-cooling. After stirring for 10 min,1,1-dichloromethyl ether (1.2 eq) was added dropwise,The reaction was carried out at 0 ° C for 3 h.To the reaction solution was added ice water, extracted with DCM, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 1,4-dimethoxy-2-naphthaldehyde.NaH was added to a 50 ml flask, under nitrogen, 5 ml of toluene and triethyl 2-phosphonopropyl ester were added and the reaction was heated to 110 ° C for 30 min. 1,4-dimethoxy-2-naphthaldehyde dissolved in 2ml of toluene, slowly dropwise to the reaction solution, continue to reflux 12h. Acidified with 2 M HC1, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Column chromatography gave Intermediate 18-2. Intermediate 18-2 was dissolved in ethanol, potassium hydroxide was added and the reaction was allowed to react for 1 h at reflux. The solvent was dried under reduced pressure to give intermediate 18-1. | |
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In dichloromethane at 25℃; for 0.5h; Inert atmosphere; | ||
6.98 g | With palladium 10% on activated carbon; hydrogen; ethyl acetate at 20℃; for 18h; | 1,4-di-O-acylonaphtalene SI-6 General procedure: A round-bottom flask was charged with 1,4-naphtoquinone (7.25 g, 45.84 mmol), which was dissolvedin AcOEt (150 mL). The flask was capped with a rubber septum and the Ar atmosphere wasestablished. The septum was removed, 10% Pd/C (0.17 g) was added and the flask was againcapped with a septum. The reaction mixture was flushed with H2 and was then stirred at roomtemperature under H2 atmosphere for 18 hrs. After completion of the reaction, Pd/C was filtered off,and the reaction mixture was filtered through silica pad with AcOEt. Concentration in vacuo afforded6.98 g (98% crude) 1,4-dihydroxynaphtalene as a brown solid which was used in the next step withoutfurther purification.1,4-dihydroxynaphtalene (6.97 g, 43.55 mmol) was dissolved in pyridine (69.95 mL) and aceticanhydride (62.57 mL) was added. The reaction was carried at room temperature for 5 hrs and thenthe reaction mixture was evaporated to dryness. Purification by column chromatography(Hexane:AcOEt = 3:1) afforded 9.33 g of 1,4-di-O-acylonaphtalene SI-6 as white powder (83% aftertwo steps). |
With sodium dihydrosulfite In diethyl ether; water monomer at 20℃; for 1h; Inert atmosphere; | ||
With palladium 10% on activated carbon; hydrogen In methanol | General method for the base-induced coupling of 1,4-dihydroxynaphthalene derivatives(8a -8c) with 2,3-dichloro-1,4-naphthoquinone (6) General procedure: To a solution of naphthoquinone 10a-c (1.0 mmol) in methanol (20 mL), 10% palladium on activated carbon (0.1% by weight) was added. The mixture was shaken under hydrogen at apressure of 20 psi for 4 hours. Palladium was then filtered off, and the solvent removed invacuo. The crude naphthol was dissolved in pyridine (10 mL) after which potassium carbonate(10 mol. equiv.), followed by 2,3-dichloro-1,4-naphthoquinone (6) (1.2 mmol), were added.The mixture was heated at 90°C for 24 hours, quenched with water (100 mL), and the organicmaterial extracted with ethyl acetate (5 x 20 mL).The organic layer was washed with a supersaturated CuSO4 solution (10 x 10 mL), brine (2 x10 mL) and water (2 x 20 mL), dried over MgSO4, filtered, and the solvent removed in vacuoto obtain the crude diether 11a-c. Isolation of the pentacyclic dinaphthofurandione derivatives 9a-9c was completed afteracidification (1N HCl, 10 mL) of the aqueous layer and collection of the resultant precipitates.Purification of the crude products was done via column chromatography using ethyl acetate hexane mixtures. | |
Multi-step reaction with 6 steps 1: pyridine; zinc powder / chloroform / 0.25 h / 70 °C / Schlenk technique; Inert atmosphere 2: sodium tetrahydridoborate / methanol 3: potassium carbonate / N,N-dimethyl-formamide / 24 h / 20 °C / Inert atmosphere 4: sodium hydroxide / ethanol / 3 h / 0 °C 5: palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous potassium acetate / N,N-dimethyl-formamide / 0.33 h / 120 °C / Microwave irradiation; Inert atmosphere 6: dihydrogen peroxide | ||
With hydrogen In tetrahydrofuran at 30℃; Flow reactor; | ||
With sodium dihydrosulfite In tetrahydrofuran; water monomer | ||
With sodium dihydrosulfite In water monomer; ethyl acetate at 20℃; for 3h; Inert atmosphere; | General procedure: In short, 1,4-Naphthoquinone 3 (5 mmol) was dissolved in EtOAc (15 mL) and anaqueous solution of sodium dithionite (2.61 g, 15 mmol, 15 mL) was added under nitrogenatmosphere at room temperature. After stirring for 3 h, the mixture was diluted with asaturated solution of ammonium chloride (15 mL) and extracted with EtOAc (3 25 mL).The combined organic layers were washed with water (50 mL) and brine (50 mL) anddried over magnesium sulfate. The solvent was removed in vacuo, and the crude 1,4-dihydroxynaphthalene 5 was directly used for the next step. | |
With sodium dihydrosulfite In ethanol; water monomer at 20℃; Inert atmosphere; | 4.1.1. General procedure for the preparation of compounds 22-23 General procedure: A mixture of naphthoquinone (14.7 mmol) and sodiumdithionite (5.0 g, 28.7 mmol) in Et2O/H2O (30/30 ml) was stirred atroom temperature under a nitrogen atmosphere overnight. Thereaction mixture was extracted by EtOAc (3 100 mL) quickly. Theorganic layers were combined, dried over anhydrous Na2SO4 andconcentrated to give a light pink solid (hydroquinone), which wasdirectly used in the next reaction without purification. | |
With sodium dihydrosulfite In tetrahydrofuran at 20℃; for 2h; | 1 Synthesis of Intermediate 1: Dissolve 15.8 g (0.1 mol) of raw material 1 in 500 mL of tetrahydrofuran, and dissolve 69.6 g (0.4 mol) of sodium dithionite in 200 mL of water to prepare a suspension, which is added to In the tetrahydrofuran containing the raw material 1, the air was isolated, and the mixture was stirred at room temperature for 2 hours to obtain a mixed solution containing the intermediate 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With potassium carbonate In acetone at 20℃; for 24h; | 1 synthesis of intermediate 1-1 18 g of 1,4-dihydroxynaphthalene was dissolved in 1 L of acetone, and then, 31 g of potassium carbonate and 11 g of methyl iodide were added thereto and then the mixture was stirred at room (e.g., ambient) temperature for 24 hours. The reaction solution was filtered, and the obtained filtrate was concentrated and the result was separation-purified by silica gel column chromatography to obtain Intermediate 1-1 (6.1 g, 45%) |
With methanol; potassium hydroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With aluminium trichloride; sodium chloride In melt at 130℃; for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In dichloromethane Flow reactor; | |
72.6% | With pyridine at 20℃; for 2h; Cooling with ice; | 17 Synthesis of 14NpOTf2 1,4-dihydroxynaphthalene 5.00g (31.2mmol, 1.0eq.) Was dissolved in pyridine 80 mL, under cooling with ice trifluoromethylsulfonate anhydride 12.6 mL (74.9 mmol, 2.4eq.) was dropped slowly.After stirring for 1 hour under ice-cooling, and the mixture was stirred at room temperature for 1 hour.Water was added, then extracted 3 times with toluene, summarized toluene layer was dried over anhydrous sodium sulfate.Aftersodium sulfate, concentrated, toluene - heptane: through silica gel column chromatography (1: 4 (volume ratio)) as eluent.The fractions containing the desired product was collected, and concentrated to give, to obtain the desired product "14NpOTf2" as a white solid (yield: 9.61g, yield: 72.6% (HPLC), purity: 99.5%) . |
With pyridine 1.) 0 deg C, 5 min, 2.) 0 deg C to r.t., 24 h; Yield given; |
With 2,4,6-trimethyl-pyridine at 20℃; for 18h; | ||
With triethylamine In dichloromethane at 0℃; for 1.5h; Inert atmosphere; | ||
With pyridine at 20℃; for 1h; Cooling with ice; | 12 Synthesis Example 12: Synthesis of Compound (B-1-5) 1,4-Dihydroxynaphthalene (5.00 g, 31.2 mmol, 1.0 eq.) was dissolved in pyridine (80 mL), and trifluoromethylsulfonic anhydride (12.6 mL, 74.9 mmol, 2.4 eq.) was slowly added dropwise under ice cooling. The mixture was stirred for one hour under ice cooling, and then the mixture was stirred at room temperature. After completion of the reaction, water was added, the mixture was extracted with toluene, and the unified toluene layer was dehydrated with anhydrous sodium sulfate. Sodium sulfate was filtered off. Thereafter, the residue was concentrated and was caused to pass through a silica gel column chromatography. By collecting and concentrating the fraction containing a desired product, a desired product “ 14NpOTf2” was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With trifluoroacetic acid at 20℃; for 0.5h; Inert atmosphere; | Synthesis of meso-1,2,3,4-tetrahydronaphthalene-1,4-diol Under Ar, a 200-mL three-necked flask was charged with 1,4-dihydroxynaphthalene (1.25 g, 7.80mmol) and CF3COOH (25 g). The suspension changed to a clear solution upon stirring at roomtemperature for 30 min. Toluene (100 mL) was added and the solvent removed under low pressure atroom temperature to afford tetralin-1,4-dione (1.14 g, 7.11 mmol, 69% yield) as a black solid. A solution of L-Selectride (1 M in THF, 17 mL) was added dropwise under Ar to a stirred, cold(-50 °C) solution of tetralin-1,4-dione (860 mg, 5.38 mmol) in DME (35 mL). After 3 h, the reactionmixture was allowed to warm to room temperature, and stirred further for 1.5 h. After addition of 36mL of a 3 N solution of NaOH and 14 mL of 30% H2O2, the mixture was stirred for 20 h and thenextracted with AcOEt (4 × 20 mL). The combined organic layers were dried over MgSO4 andvolatiles were removed under reduced pressure. Recrystallization from hot AcOEt gavemeso-1,2,3,4-tetrahydronaphthalene-1,4-diol as red purple crystals (79.5 mg, 9% yield). |
With trifluoroacetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.9% | With potassium carbonate In acetone for 4h; Heating; | |
With potassium hydroxide In water; acetone | 3.a a) a) 1-Benzyloxy-4-hydroxynaphthalene 23.7 g. (0.147 mole) 1,4-Dihydroxynaphthalene (purified by shaking an ethereal solution thereof with sodium dithionite solution) are dissolved in 200 ml. acetone. After adding 20.3 g. (0.147 mole) of pulverised potassium hydroxide and heating to reflux temperature, 18.6 g. (16.9 ml.) benzyl chloride are added dropwise thereto in the course of 60 minutes. The reaction mixture is thereafter heated under reflux for 4 hours while stirring, evaporated and the residue is mixed with 100 ml. water and extracted with diethyl ether. The ethereal solution is dried with anhydrous magnesium sulphate, filtered and evaporated. The tar-like residue is extracted with cyclohexane. The combined extracts are cooled, considerable amounts of a tarry product thereby first separating out. Thereafter, the pure compound crystallises out. It is washed with cyclohexane and dried. Yield 4.3 g. (11.9% of theory); m.p. 118°-119° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.3% | With potassium carbonate; In N,N-dimethyl-formamide; at 25℃; for 20h;Inert atmosphere; | A four-necked reactor equipped with a thermometer was charged with 20.0 g (125 mmol) of 1,4-dihydroxynaphthalene and 200 ml of N,N-dimethylformamide (DMF) under a nitrogen stream to prepare a homogeneous solution. After the addition of 51.8 g (375 mmol) of potassium carbonate and 19.4 ml (312 mmol) of methyl iodide to the solution, the mixture was stirred at 25 C. for 20 hours. After completion of the reaction, the reaction mixture was filtered through celite. The filtrate was added to 500 ml of water, and extracted with 500 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was separated by filtration. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a white solid. The white solid was recrystallized from n-hexane (125 ml) to obtain 20.3 g of an intermediate F as colorless crystals (yield: 86.3%). [0243] The structure of the target product was identified by 1H-NMR. [0244] 1H-NMR (500 MHz, CDCl3, TMS, delta ppm): 8.19-8.22 (m, 2H), 7.52-7.48 (m, 2H), 6.69 (s, 2H), 3.95 (s, 6H) |
86.3% | With potassium carbonate; In N,N-dimethyl-formamide; at 25℃; for 20h;Inert atmosphere; | Step 3: Synthesis of Intermediate F A four-necked reactor equipped with a thermometer was charged with 20.0 g (125 mmol) of 1,4-dihydroxynaphthalene and 200 ml of N,N-dimethylformamide (DMF) under a nitrogen stream to prepare a homogeneous solution. After the addition of 51.8 g (375 mmol) of potassium carbonate and 19.4 ml (312 mmol) of methyl iodide, the mixture was stirred at 25 C. for 20 hours. After completion of the reaction, the reaction mixture was filtered through celite. The filtrate was added to 500 ml of water, and extracted with 500 ml of ethyl acetate. After drying the ethyl acetate layer over anhydrous sodium sulfate, sodium sulfate was separated by filtration. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a white solid. The white solid was recrystallized from n-hexane (125 ml) to obtain 20.3 g of an intermediate F as colorless crystals (yield: 86.3%). The structure of the target product was identified by 1H-NMR. 1H-NMR (500 MHz, CDCl3, TMS, delta ppm): 8.19-8.22 (m, 2H), 7.52-7.48 (m, 2H), 6.69 (s, 2H), 3.95 (s, 6H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With pyridine; thionyl chloride; sulfinylcarbamic acid ethyl ester In benzene for 2h; Heating; | |
Multi-step reaction with 5 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 71 percent / SCl2, S2Cl2, pyridine / benzene / 1.5 h / Heating 3: 88 percent / SOCl2, pyridine / benzene / 3.5 h / Heating 4: 72 percent / benzene / 3 h / Heating 5: 68 percent / ethyl N-sulfinylcarbamate, SOCl2, pyridine / benzene / 2 h | ||
Multi-step reaction with 5 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 71 percent / SCl2, S2Cl2, pyridine / benzene / 1.5 h / Heating 3: 88 percent / SOCl2, pyridine / benzene / 3.5 h / Heating 4: 75 percent / benzene / 2 h / Heating 5: 68 percent / ethyl N-sulfinylcarbamate, SOCl2, pyridine / benzene / 2 h |
Multi-step reaction with 4 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 71 percent / SCl2, S2Cl2, pyridine / benzene / 1.5 h / Heating 3: 88 percent / SOCl2, pyridine / benzene / 3.5 h / Heating 4: 80 percent / S4N4, pyridine / benzene / 24 h / Heating | ||
Multi-step reaction with 3 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 87 percent / benzene / 2 h / Heating 3: 68 percent / ethyl N-sulfinylcarbamate, SOCl2, pyridine / benzene / 2 h | ||
Multi-step reaction with 3 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 72 percent / benzene / 2 h / Heating 3: 68 percent / ethyl N-sulfinylcarbamate, SOCl2, pyridine / benzene / 2 h | ||
Multi-step reaction with 2 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 90 percent / (NSCl)3 / benzene / 2 h / Heating | ||
Multi-step reaction with 4 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 87 percent / SOCl2, pyridine / benzene / 3.5 h / Heating 3: 72 percent / benzene / 3 h / Heating 4: 68 percent / ethyl N-sulfinylcarbamate, SOCl2, pyridine / benzene / 2 h | ||
Multi-step reaction with 4 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 87 percent / SOCl2, pyridine / benzene / 3.5 h / Heating 3: 75 percent / benzene / 2 h / Heating 4: 68 percent / ethyl N-sulfinylcarbamate, SOCl2, pyridine / benzene / 2 h | ||
Multi-step reaction with 3 steps 1: 92 percent / SOCl2 / benzene / 2 h / Heating 2: 87 percent / SOCl2, pyridine / benzene / 3.5 h / Heating 3: 80 percent / S4N4, pyridine / benzene / 24 h / Heating | ||
Multi-step reaction with 3 steps 1: 74 percent / SOCl2, pyridine / benzene / 3 h / Heating 2: 72 percent / benzene / 3 h / Heating 3: 68 percent / ethyl N-sulfinylcarbamate, SOCl2, pyridine / benzene / 2 h | ||
Multi-step reaction with 3 steps 1: 74 percent / SOCl2, pyridine / benzene / 3 h / Heating 2: 75 percent / benzene / 2 h / Heating 3: 68 percent / ethyl N-sulfinylcarbamate, SOCl2, pyridine / benzene / 2 h | ||
Multi-step reaction with 2 steps 1: 74 percent / SOCl2, pyridine / benzene / 3 h / Heating 2: 80 percent / S4N4, pyridine / benzene / 24 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium carbonate In 2,2,2-trifluoroethanol | |
72.7% | With water at 250℃; for 0.333333h; Inert atmosphere; Supercritical conditions; | |
With sodium hydroxide at 140℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With lipase of Pseudomonas sp; water In various solvent(s) at 25℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With [O=P(2-py)3W(CO)(NO)2](BF4)2 In water at 20℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37.9% | In dichloromethane at 25℃; for 16h; | 5 A mixture of 1,4-dihydroxynaphthalene (40.5 g, 0.253 mol), 3.4-dihydro-2H-pyran (106.7 g. 1.268 mol), and p-toluenesulfonic acid monohydrate (0.48 g) in degassed CH2Cl2 (960 mL) was stirred at 25°C for sixteen hours. The mixture was diluted with Et2O (1.2 L), washed in succession with saturated aqueous NaHCO3 (400 mL), H2O (400 mL), brine (400 mL), dried over MgSO4, and spin-evaporated in vacuo to an oil. The oil was chromatographed on a silica gel column (2.0 kg), packed in and eluted with CH2Cl2 (20.0 L). Appropriate fractions as determined by TLC were combined and spin-evaporated in vacuo to give 31.5 g (37.9%) of product as a viscous oil. Additional reactions were performed to give a total of 81.0 g of product suitable for further transformation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With carbon dioxide; sodium methylate; | EXAMPLE 1 16 Parts of 1,4-dihydroxynaphthalene was added to 100 parts of <strong>[13588-28-8]dipropylene glycol monomethyl ether</strong> in a reaction vessel provided with a stirrer under a nitrogen atmosphere at room temperature. 42.5 Parts of 28% sodium methylate was added dropwise thereto. Then the reaction mixture was heated to 180 C. and maintained at this temperature for 1 hour. During this period, 36 parts of a distillate mainly composed of methanol was removed out of the reaction system. After cooling to 110 C., carbon dioxide gas was blown into the reaction mixture under atmospheric pressure. Although the absorption of the carbon dioxide gas was completed within 15 minutes, carbon dioxide gas was further blown for additional 15 minutes. 1,4-Dihydroxy-2-naphthoic acid produced in the reaction mixture was isolated in the following manner: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium hydroxide; In water; toluene; | EXAMPLE 3 A reaction vessel was charged with 60 g of toluene, 50 g of water, 37.3 g of <strong>[13852-51-2]5-chloro-2-methyl-p-nitroaniline</strong>, 6 g of sodium hydroxide and 0.3 g of 1,4-naphthalenediol, and then the same procedure as in Example 1 was followed, to obtain 29.4 g of 2-chloro-5-methyl-p-phenylenediamine. Yield: 94% Purity determined by G.C. analysis: 99.8% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | In chloroform | 22 Oxidation of 1,4-Dihydroxynaphthalene EXAMPLE 22 Oxidation of 1,4-Dihydroxynaphthalene 1,4-Dihydroxynaphthalene (80 mg, 0.50 mmol) and bis-(p-methoxyphenyl)-telluroxide (196 mg, 0.55 mmol) were stirred in chloroform (4 ml) at room temperature under argon for 1 h. The reaction mixture was concentrated by evaporation of the solvent under reduced pressure and p.l.c. (benzene-ethyl acetate 9:1) gave bis-(p-methoxyphenyl)-telluride (96 mg, 56%) and p-naphthoquinone (77 mg, 97%) as an olive green solid m.p. 122°-125° which on recrystallisation from ethanol gave yellow needles (60 mg, 76%) m.p. 125°-126° (lit., 126) δ(CDCl3) 8.27-7.67 (4H, m), and 7.00 (2H, S). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With o-tetrachloroquinone; dimer of (η(5)-cyclopentadienyl)tricarbonylmolybdenum In chlorobenzene at 150℃; for 1h; Inert atmosphere; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 83% 2: 7 %Spectr. | In acetone Irradiation; Inert atmosphere; Flow reactor; Green chemistry; | Solar Continuous-Flow Operation in Concentrated Sunlight Photoacylations of 1,4-Naphthoquinone General procedure: The solar reactor was positioned vertically to the sun and the receiver tube was placed in the focal point of the parabolic concentrator. Cooling water was passed through the central glass tube. A solution of 1,4-naphthoquinone (1a, 2 mmol) andaldehyde (2a-e, 10 mmol) in acetone (100 mL) in a 250-mL amber round-bottom flask was degassed with nitrogen for 5 min and pumped through the solar flow reactor at a flow rate of 0.75mL min1. The reaction mixture and , 75mL of fresh acetone were collected in a 250-mL amber round-bottom flask. The solvent was removed by careful rotary evaporation and the residue was dried under vacuum. The degree of conversion was subsequently determined by 1H NMR analysis using baseline separated signals. The crude photoproducts obtained using aliphatic aldehydes (3a-c) were purified by washing with warm distilled water (~50 °C) in an ultrasound bath and subsequent recrystallization. The products obtained from aromatic aldehydes (3d and 3e) were purified by column chromatography and successive recrystallization instead. |
40% | With 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide for 16h; Irradiation; Inert atmosphere; chemoselective reaction; | |
In acetone; iso-butanol for 14.5h; Irradiation; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 12h;Inert atmosphere; | General procedure: Hydroquinone or 1,4-dihydroxynaphthalene (5.0 mmol) and the corresponding dibromide (5.0 mmol) in dehydrated DMF (30 mL) were added dropwise over 12 h to a suspension of K2CO3 (12.5 mmol) in dehydrated DMF (50 mL) at 140 C. The reaction mixture was cooled to rt and filtered with Celite. The filtrate was treated with saturated NH4Cl aqueous solution and extracted with ethyl acetate. The organic layer was washed with water and brine. The extract was dried over Na2SO4 and evaporated under reduced pressure. The residue was filtered through a short plug of silica gel with dichloromethane and the filtrate was evaporated under reduced pressure. The crude products were purified by flash column chromatography (hexane/AcOEt=30/1∼20/1) and GPC (1,2-dichloroethane) to give dioxaparacyclophanes 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With sodium hydroxide In 1,4-dioxane at 20℃; for 12h; | 1 [0119] 1,4-Naphthalene propanesulfonate wall (figure 2). Into a solution of 1,4- dihydroxynaphathelene (2.0 g, 12.5 mmol) in NaOH (10 wt%, 16 mL), a solution of propanesultone (3.8 g, 31.2 mmol) in 1,4-dioxane (24 mL) was added. This solution was stirred at RT for 12 h. After filtration, the solid was dissolved in H20 (10 mL) and then precipitated with MeCN (60 mL) to yield a blue solid (1.5 g, 3.3 mmol, 27%). M.p. > 227 °C (dec). IR (ATR, cm"1): 2988w, 2902w, 1597w, 1462w, 1377w, 1273m, 1240m, 1222m, 1183s, 1155m, 1100m, 946s, 800w, 765m, 613m. 1H NMR (600 MHz, D20): 8.01 (m, 2H), 7.43 (m, 2H), 6.63 (s, 2H), 4.02 (t, 4H), 3.02 (t, 4H), 2.16 (m, 4H). 13C NMR (125 MHz, D20, 1,4-dioxane as internal reference): δ 148.0, 126.4, 125.9, 121.4, 106.3, 67.5, 48.1, 24.2. High-Res MS (ESI): m/z 427.0528 ([M +Na]+), calculated 427.0497. |
27% | With sodium hydroxide In 1,4-dioxane at 20℃; | |
27% | With sodium hydroxide In 1,4-dioxane at 20℃; for 12h; | Into a solution of 1,4- dihydroxynaphathelene (2.0 g, 12.5 mmol) in NaOH (10 wt%, 16 mL), a solution of propanesultone (3.8 g, 31.2 mmol) in 1,4-dioxane (24 mL) was added. This solution was stirred at RT for 12 h. After filtration, the solid was dissolved in H2O (10 mL) and then precipitated with MeCN (60 mL) to yield a blue solid (1.5 g, 3.3 mmol, 27%). M.p. > 227 oC (dec.). IR (ATR, cm-1): 2988w, 2902w, 1597w, 1462w, 1377w, 1273m, 1240m, 1222m, 1183s, 1155m, 1100m, 946s, 800w, 765m, 613m.1H NMR (600 MHz, D2O): 8.01 (m, 2H), 7.43 (m, 2H), 6.63 (s, 2H), 4.02 (t, 4H), 3.02 (t, 4H), 2.16 (m, 4H).13C NMR (125 MHz, D2O, 1,4-dioxane as internal reference): δ 148.0, 126.4, 125.9, 121.4, 106.3, 67.5, 48.1, 24.2. High-Res MS (ESI): m/z 427.0528 ([M +Na]+), calculated 427.0497 |
27% | Stage #1: 1,4-Dihydroxynaphthalene With sodium thiosulfate In diethyl ether at 30℃; for 1h; Inert atmosphere; Stage #2: 1,3-propanesultone With sodium hydroxide In 1,4-dioxane at 20℃; for 12h; | 1.4 (4) Synthesis of the naphthalene ring side arm of sodium sulfonate: A solution of 10% sodium thiosulfate (20 mL) was added to a solution of 1,4-naphthoquinone (150 mg, 948 μmol) in diethyl ether (20 mL). The reaction solution was vigorously stirred under argon protection at 30 °C for 1 h. After the color of the yellow ether layer was removed, the reaction mixture was extracted with ethyl acetate (50 mL, EtOAc) Drying over magnesium sulfate gave a crude 1,4-naphthalenediol. Add propanesultone (3.8 g, 31.2 mmol) to a solution of 1,4-naphthalenediol (2.0 g, 12.5 mmol) in NaOH (10 wt%, 16 mL) a solution of 1,4-dioxane (24 mL), The reaction solution was stirred at room temperature for 12 h and then filtered. The resulting solid was dissolved in 10 mL of water. Precipitate with 60 mL of acetonitrile to give a blue solid (1.5 g, 3.3 mmol, 27%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In ethanol for 18h; Reflux; | 9 Example 9:2-Amino-6-hydroxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-benzo[h]chromene-3-carbonitrile (9)(9)1,4-Dihydroxy-naphthalene (704 mg, 4.4 mmol), 3-bromo-4,5-dimethoxy-benz-aldehyde (1077 mg, 4.4 mmol) and malononitrile (295 mg, 4.4 mmol) were taken in 40 ml ethanol at room temperature, charged with DABCO (48.4 μ, 1.46 mmol) and then refluxed with stirring under LC- MS control for 18 h. The reaction mixture was then cooled down to room temperature. The mixture was diluted with water to about 100 ml, stirred at room temperature for 1 h and the precipitates were separated by filtration. It was washed well with 50 % aqueous ethanol and dried under vacuum (1.68 g, 3.7 mmol, 84 %). |
84% | With 1,4-diaza-bicyclo[2.2.2]octane In ethanol at 20 - 80℃; for 18h; | 9 1,4-Dihydroxy-naphthalene (704 mg, 4.4 mmol), 3-bromo-4,5-dimethoxy-benz-aldehyde (1077 mg, 4.4 mmol) and malononitrile (295 mg, 4.4 mmol) were taken in 40 ml ethanol at room temperature, charged with DABCO (48.4 μ, 1.46 mmol) and then refluxed with stirring under LC- MS control for 18 h. The reaction mixture was then cooled down to room temperature. The mixture was diluted with water to about 100 ml, stirred at room temperature for 1 h and the precipitates were separated by filtration. It was washed well with 50 % aqueous ethanol and dried under vacuum (1.68 g, 3.7 mmol, 84 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | With novozyme 51003 In water; N,N-dimethyl-formamide at 35℃; for 48h; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With ammonium peroxydisulfate; iodine; iron In 1,2-dichloro-ethane at 120℃; for 24h; Sealed tube; | |
40% | With palladium(II) acetylacetonate; dimethyl sulfoxide; silver carbonate; Trimethylacetic acid at 140℃; for 24h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
22% | With palladium(II) acetylacetonate; dimethyl sulfoxide; silver carbonate; Trimethylacetic acid In 1,2-dichloro-ethane at 140℃; for 24h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid In benzene at 80℃; for 1h; Inert atmosphere; | Synthesis of 1,4-bisdecanethionaphtalene, (NpDDT). 1,4-bisdecanethionaphtalene. NpDDT, was prepared by the similar method as previously reported [21]. Under N2 atmosphere, 1,4-dihydroxynaphthalene (0.81 g, 5 mmol), p-toluenesulfonic acid (0.48 g, 2.5 mmol) and 1,10-decanedithiol (10 mL, 46 mmol) were dissolved into benzene (50 mL), and the mixture was refluxed at 80 °C for 1 h. After aqueous workup, the product was purified by column chromatography on silica gel using ethyl acetate as an eluent. The collected product was crystallized from a mixture of ethyl acetate and hexane to give NpDDT as a white solid. FT-IR spectrum (KBr): 2924, 2849 (C-H) cm-1, 2567 (S-H) cm-1, 1564 (C=C of Ar) cm-1, 1466 (C-H) cm-1. 1H NMR spectrum (ppm, CDCl3): 1.2-1.4 (m, 26H), 1.5-1.7 (m, 8H), 2.5-2.6 (m, 4H), 2.9-3.0 (m, 4H), 7.5 (s, 2H), 7.5-7.6 (m, 2H), 8.4-8.5 (m, 2H). Anal. Calcd for C30H48S4: C, 67.10; H, 9.01; N, 0; S, 23.89%. Found: C, 66.87, H, 9.06, N, 0.00, S, 24.00%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h; Inert atmosphere; | 4.1.2. Synthesis of naphthalene-1,4-diyl diacetate (2) To a solution of 1,4-dihydroxynaphthalene (1, 16.02 g, 0.10 mol) in CH2Cl2 (150 mL) was added N,N-diisopropylethylamine (DIPEA, 52.3 mL, 0.30 mol) and 4-(dimethylamino)pyridine (DMAP, 2.44 g, 0.02 mol) at room temperature. The reaction mixture was stirred at room temperature for 30 min, and then, acetyl chloride (14.9 mL, 0.21 mol) was added incrementally by syringe. Reaction progress was monitored by TLC. After all the starting material was consumed, the reaction mixture was quenched with water (100 mL) and the aqueous solution was extracted with CH2Cl2 (100 mL x 3). Combined organic extracts were washed with water, dried (MgSO4), and evaporated in vacuo. Flash chromatography on silica gel using hexane/ethyl acetate (4:1) as eluant afforded 2 (23.4 g, 96%) as a yellow solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | Stage #1: 1,4-Dihydroxynaphthalene With 18-crown-6 ether; potassium hydride In tetrahydrofuran at 0℃; for 0.166667h; Inert atmosphere; Darkness; Stage #2: carbonic acid dimethyl ester In tetrahydrofuran at 0 - 20℃; for 10h; | Methyl 1,4-Dihydroxy-2-naphtoate (4a). To a 1,4-naphtoquinone(2) (200 mg, 1.26 mmol) in MeOH (10 mL) was added Na2S2O4 (330 mg, 1.90 mmol) with ascorbic acid (178mg, 1.01 mmol) under nitrogen atmosphere and stirred for 5h at rt under light protection. After MeOH was removed by evaporation in the reaction, potassium hydride (159 mg, 1.39 mmol) and 18-crown-6 (506 mg, 1.39 mmol) were added slowly to this reaction mixture with THF (20 mL) at 0 oC and stirred for 10 min. Dimethyl carbonate (0.117 mL, 1.39 mmol) was added slowly to this reaction mixture at 0 oC and stirred for 10 h at rt. The reaction mixture was filtered with Celite 545, extracted with EtOAc, washed with brine, dried over anhydrous MgSO4, concentrated in vacuo, and purified by silica gel flash column chromatography (PetEther:EtOAc= 25:1) to give a yellow solid (112 mg, 41%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With laccase from Trametes Villosa; oxygen In methanol at 22℃; for 16h; Green chemistry; Enzymatic reaction; | 4.5 2.3 General procedure for the laccase-catalyzed reaction of 1,2-ethanedithiol 1 with substituted hydroquinones 2 General procedure: The hydroquinone 2 (0.50 mmol) was added to a 50 mL round bottom flask equipped with a stir bar followed by 15 mL of solvent and the mixture was stirred. Once the solid had dissolved, 1,2-ethanedithiol 1 (2.50 mmol) was introduced, followed by 50 U of laccase. The reaction mixture was stirred at room temperature (22 °C) for 16 h whilst O2 was bubbled through. The reaction progress was monitored by TLC using silica gel coated on aluminum sheets as the stationary phase, 1:1 EtOAc/hexane (v:v) mixture as the mobile phase, and iodine vapor as the staining agent. Once the reaction was complete, the reaction mixture was extracted with EtOAc (3× 20 mL), dried over MgSO4, and the solvent removed via rotary evaporation. The crude extract was purified via column chromatography using silica gel as the stationary phase and 1:1 EtOAc/hexane (v:v) mixture as the mobile phase to obtain the desired products. The products were characterized using HRMS, 1H NMR, 13C NMR, and FTIR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Stage #1: 3-mercaptopropionic acid; [1,4]naphthoquinone In ethanol at 20℃; for 24h; Stage #2: With lead dioxide In chloroform at 20℃; for 4h; | 3-[(1,4-dioxo-1,4-dihydronaphthalene-2-yl)thio]propionicacid (1). A solution of 1.0 g b-thiopropionicacid (0.009 mol) in 7 ml of ethanol was added to the suspension of 3.0 g naphthoquinone(0.019 mol) in 40 ml of ethanol, and the mixture was stirred at room temperature for 24h. The precipitate was filtered off and suspended in 50 ml of chloroform. The suspension was mixed with 2.0 g PbO2 (0.008 mol) and stirred at room temperature for 4 h. The excess of the oxidant was filtered off, the solvent was removed under reduced pressure at room temperature. The crude material was purified by column chromatography (SiO2, chloroform as eluent). Thedark orange product was washed with hexane in Soxhlet's extraction apparatus.The yellow 3-[(1,4-dioxo-1,4-dihydronaphthalene-2-yl)thio]propionicacid (1) was additionally purified through recrystallization from methanol [2.57 g, 52%yield, mp 185-188 °].1 NMR (DMSO-d6, dH) 2.64 (t, 2, 2,J=6.7 Hz), 3.03 (t, 2, SCH2, J=6.7 Hz), 6.60 (s, 1, 2), 7.73-7.80 (m, 2, 6, 7), 7.83-7.87 (m, 2, 5, 8).13C NMR (DMSO-d6, dC): 24.9(S2).32.1 (2), 126.5 (3), 126.8, 127.5 (5,8), 131.6, 131.9 (9,10), 134.2, 135,3(6,7), 153.9 (2),173.2 (2), 181.4,182.2 (1,4). IR (KBr, n/cm-1): 3047 (), 1726 (), 1668, 1560 (-C=C-CO). HPLC-MS: experimental [M+H]+241.050, [M+Na]+ 263.030. Calculated: [M+H]+ 241.055,[M+Na]+ 263.037. 1310O4S. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With Trametes villosa laccase; oxygen In methanol at 22℃; for 12h; Enzymatic reaction; | 3,4-Dihydro-2H-naphtho[2,3-b][1,4]thiazine-5,10-dione 192.9 mg (2.50 mmol) of cysteamine (8) was added to a 50mL round-bottom flask equipped with a stir bar. 8.5 mL 0.10 M sodium acetate buffer pH 5.0 was added followed by 33.1 μL (50U) of laccase solution and the mixture was stirred. Then, 80.1 mg (0.50 mmol) of 2a was dissolved in 1.5 mL MeOH and added dropwise to the mixture. The reaction mixture was allowed to stirat rt for 12 h. The precipitate was then filtered, washed with deionized water, and left to dry in a fume hood overnight. The product was purified via preparative layer chromatography using silica gel coated on glass plates as the stationary phase and dichloromethane containing 1% MeOH (v:v) as the mobile phase.Yield of 9: 39.3 mg (34%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | Stage #1: 1,4-Dihydroxynaphthalene With Trametes villosa laccase; oxygen In methanol at 22℃; for 2h; Enzymatic reaction; Stage #2: 2-amino-benzenethiol In methanol at 22℃; for 4h; Enzymatic reaction; | 5H-Benzo[a]phenothiazin-5-one (3a) Method B: 100.1 mg (0.625 mmol) of 2a was dissolved in 1.5 mL MeOH and added dropwise to 8.5 mL 0.10 M sodium acetate buffer pH 5.0 containing 33.1 μL (50 U) of laccase solution while stirring at rt in a 50 mL round-bottom flask. After 2 h, 53.5 μL (62.6 mg, 0.50 mmol) of 1 was added to the mixture, and the reaction was allowed to stir for an additional 4 h. Work-up and purification as in Method A. Yield of 3a: 26.3 mg (20%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 6.7% 2: 15.4% | With peroxygenase; dihydrogen peroxide In acetonitrile at 20℃; for 0.416667h; Enzymatic reaction; | 12 Example 12 Oxidation of Naphthalene Oxidations of 1 mM naphthalene with 1 mM H2O2 were carried out with 20% acetonitrile and 20 mM acetate (pH 3-5), phosphate (pH 6-7) or borate buffer (pH 8) at specified pH values using 0.01 mg/mL of purified peroxygenase (mature peroxygenase encoded by SEQ ID NO: 1) in a total reaction volume of 1 mL. Reactions were performed at room temperature for 25 minutes and samples were then inactivated with 1 μL of catalase (Terminox Ultra 50 L, Novozymes). (0302) Samples were analyzed on an Agilent 1200 HPLC system equipped with a Diode Array Detector (Agilent, Santa Clara Calif., USA) and separated on a Gemini C6-Phenyl (110 , 2×150 mm, 3 μm) column from Phenomenex (Torrance Calif., USA) thermostated at 40° C. Two mobile phases were used: (A) 0.1% formic acid, and (B) 0.1% formic acid in acetonitrile. (0303) Separations were run using stepwise gradient starting with 30% B held for 0.5 min, then increasing to 50% B within 3.5 min and then increasing to 60% B within 5 min with a constant flow rate of 0.4 mL/min. (0304) Naphthalene and its oxidation products 1-naphthol, 2-naphthol, 1,4-naphthoquinone and naphthalene-1,4-diol were identified using authentic standards, based on their retention times and UV absorption spectra (210 nm or 204 nm). Quantification was done based on external calibration of authentic standards except for 1,4-naphthoquinone that was quantified using naphthalene-1,4-diol as a standard. (0305) The peroxygenase oxidised naphthalene yielding multiple products 1-naphthol, 2-naphthol, 1,4-naphthoquinone, naphthalene-1,4-diol and some unidentified products. [table-us-00013-en] TABLE 12 Naphthalene oxidation product yields at various pH. Yield (%) Total pH NPD NPQ 2-NOL 1-NOL unknown product 3 15.4 2.5 1.1 6.7 0.0 25.7 5 8.4 1.3 1.0 21.0 14.4 46.1 6 8.8 1.4 0.5 20.7 14.4 45.7 7 10.0 1.5 0.0 20.2 15.3 47.0 8 8.2 1.5 0.0 16.7 18.1 44.4 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With Calcium tetrakis(pentafluorophenyl)borate; dihydrogen peroxide; oxalic acid; calcium iodide In 1,2-dichloro-ethane at 50℃; for 7.5h; | 5 In Example 5, according to the above formula were performed tandem reaction of oxidative coupling. In the reaction vessel, at room temperature, is a substrate 1,4-naphthalene diol (32mg, 0.2mmol) and 4 equivalents with respect to it 1,3-dimethoxybenzene (110.6mg, 0.8mmol), with respect to the substrate 1mol% of Ca [B (C6F5) 4] 2 (4.1mg, 0.002mmol), 10mol% of oxalic acid (1.8mg, 0.02mmol), 5-mol% of calcium iodide (3mg, 0. 01mmol), and was added dichloroethane (1 mL) as a solvent, then 3 equivalents (30 wt% aqueous solution, Nacalai Co., 61MyuL, was added aqueous hydrogen peroxide of 0.6 mmol). Thereafter, the reaction solution in the 50 , and stirred for 7.5 hours, the reaction was carried out. After completion of the reaction, the reaction solution is cooled to room temperature, the same work-up (extraction, solvent evaporation and purification) of Experimental Example 3, a coupling product of 2,3-bis (2,4-dimethoxyphenyl) naphthalene the 1,4-dione as a red solid (72.4mg, 0.17mmol, 84% yield). In Example 5, first, 1,4-naphthaleneDiol is oxidized 1,4-naphthoquinone is produced, then 2 to locations 1,3-dimethoxybenzene coupling to 2 substituents 1,4-naphthalene diol 1,4-naphthoquinone is produced, the final product was obtained the diol is oxidized. The analytical data of the obtained product are shown below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With dihydrogen peroxide; oxalic acid; lithium tetrakis(pentafluorophenyl)borate; calcium iodide In 1,2-dichloro-ethane at 20℃; for 32h; | 10 In Example 10, according to the above formula were performed tandem reaction of oxidative coupling. In the reaction vessel, at room temperature, is a substrate of 1,4-naphthalene diol (160.2mg, 1mmol) and contrast 2 equivalents of 2-methylindole (262.4mg, 2mmol), 1mol% with respect to the substrate of Li [B (C6F5) 4] (9.5mg, 0.01mmol), 10mol% of oxalic acid (9mg, 0.1mmol), 5mol% of calcium iodide (15mg, 0.05mmol), and a solvent dichloroethane ( 10mL) was added, then 2.2 eq (30 wt% aqueous solution, Nacalai Co., 220MyuL, was added aqueous hydrogen peroxide of 2.2 mmol). Then, stirred for 32 hours at room temperature, the reaction was carried out. After completion of the reaction, the same post-treatment (extraction, solvent evaporation and purification) of Experimental Example 3, a coupling product 2- (2-methyl -1H- indol-3-yl) naphthalene-1,4 - to give the dione as a purple solid (251.4mg, 0.88mmol, 88% yield). The analytical data of the obtained product are shown below. |
88% | With lithium(etherate)2.5 tetrakis(pentafluorophenyl)borate; dihydrogen peroxide; oxalic acid; calcium iodide In water; 1,2-dichloro-ethane at 20℃; for 32h; | |
87% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6 g | With sodium hydroxide In toluene at 5℃; Inert atmosphere; | 1 Synthesis of 4-ethoxy-1-naphthyl methacrylate thermometer, in a three-necked flask with a stirrer 200ml, water 75.0ml, toluene 15.0ml, sodium hydroxide 1.4g (35.0 mmol) , and 1,4-naphthalene diol was charged with 5.0g (31.3 mmol). Then, under a nitrogen gas atmosphere, cooling and stirring, it was dropped methacrylic acid chloride 3.5g (33.0mmol). During this period, maintaining the internal temperature of the reaction vessel to 5 or less. From the middle of dropping, the precipitation of a large amount of crystals were observed. Deposition of a large amount of post-stirring drop 30 minutes crystal was observed. Suction filtering the reaction mixture, washed with water funnel over 30 ml, further washed with toluene 30 ml, to give 4-hydroxy-1 off-white crystals 6.0g naphthyl methacrylate (26.3 mmol). The 4-hydroxy-1-naphthyl methacrylate 4.56 g (20 mmol) and dimethylacetamide 18 ml, the 3.39g of diethyl sulfate (22 mmol), stirrer, in a three-necked flask 100ml with a thermometer, a nitrogen atmosphere was charged, It became a stirred place colorless solution. Then, while cooling with ice water, water was added 10ml solution of sodium hydroxide 088g (22 mmol). It flask bottom in a thin red syrup-like oil of the solution at the same time as the addition. 1 hour was allowed to stand, the supernatant was discarded, the oil-like substance is washed twice with water 10ml, to dissolve the soluble component in addition methanol 30ml. Methanol solution was concentrated to give 4-ethoxy-1-methacrylate 3.0g of (11.7 mmol). The yield based on the starting material 4-hydroxy-1-naphthyl methacrylate was 58 mol%. |
6 g | With sodium hydroxide In water; toluene at 5℃; for 0.5h; Inert atmosphere; | 1 thermometer,In a three-necked flask of 200ml with a stirrer,Water 75.0ml,Toluene 15.0ml,Sodium hydroxide 1.4g (35.0 mmol),And 1,4-naphthalene diol was charged with 5.0g (31.3 mmol).next,Under a nitrogen gas atmosphere,While cooling and stirring,It was added dropwise methacryloyl chloride 3.5g (33.0mmol).During this time,The internal temperature of the reaction vessel was maintained at 5 or less.From the middle of the drip,Deposition of a large amount of crystals were observed.Deposition of a large amount of post-stirring drop 30 minutes crystal was observed.Suction filtering the reaction mixture,Washed with water of the funnel on the 30ml,Further washed with toluene of 30ml,4-hydroxy-1-naphthyl methacrylateofOff-white crystals were obtained 6.0g of (26.3 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With oxygen; toluene-4-sulfonic acid In 1,2-dichloro-ethane at 83℃; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With methanesulfonic acid; trifluoroacetic acid at 20℃; for 20h; regioselective reaction; | General Procedure for the Synthesis of 5-Carboxy-SNAFLs. General procedure: 4-(2,4-Dihydroxybenzoyl)isophthalic acid (1) (500 mg, 1.65 mmol) and the appropriate dihydroxynaphthalene (275 mg, 1.75 mmol) were dissolved in methanesulfonic acid (10 mL) or a mixture of TFA (5 mL) and methanesulfonic acid (5 mL), and stirred at room temperature overnight. The reaction was quenched with H2O (25 mL) and the resulting dark purple precipitate collected by centrifugation. After decantation, the precipitate was dissolved in NaOH(aq) (2 M, 15 mL) and precipitated with HCl (aq) (2 M, 20 mL). After decantation, the precipitate was washed with H2O (2 x 35 mL), dissolved in EtOH (10 mL) and precipitated with H2O. After decantation and washing with H2O (2 x 35 mL), the compound was dried in vacuo yielding a dark purple powder. If required, further purification by silica gel dry column vacuum chromatography (2% AcOH in CH2Cl2/MeOH with 5% increments) was performed by dissolution of the compound in MeOH and NaOH (aq) (12 M, 2 drops) and evaporation onto Celite in vacuo. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With tert.-butylhydroperoxide; Cu(2+)*2CHF3O3S; palladium diacetate In decane at 64 - 65℃; for 6h; Inert atmosphere; | 1.17 General procedure: To a reaction flask dried in an oven under a nitrogen atmosphere Pd (OAc) 2 (5.6 mg, 5 mol%), Cu (OTf) 2 (45 mg, 25 mol%), 2,4-dihydroxyacrylcarbonyl (Or naphthol and 1,4-dihydroxynaphthalene) (5.0 mmol), THF (or ethers and alcohols) (5.0 mL), and t-butyl hydroperoxide (TBHP, 5.0-6.0 M in decane, 0.1 mL, 0.6 mmol).The reaction mixture was stirred on an oil bath at 65°C for 2-24 h. Subsequently, the volatiles were removed under vacuum and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With tert.-butylhydroperoxide; Cu(2+)*2CHF3O3S; palladium diacetate In decane at 64 - 65℃; for 4h; Inert atmosphere; | 1.18 General procedure: To a reaction flask dried in an oven under a nitrogen atmosphere Pd (OAc) 2 (5.6 mg, 5 mol%), Cu (OTf) 2 (45 mg, 25 mol%), 2,4-dihydroxyacrylcarbonyl (Or naphthol and 1,4-dihydroxynaphthalene) (5.0 mmol), THF (or ethers and alcohols) (5.0 mL), and t-butyl hydroperoxide (TBHP, 5.0-6.0 M in decane, 0.1 mL, 0.6 mmol).The reaction mixture was stirred on an oil bath at 65°C for 2-24 h. Subsequently, the volatiles were removed under vacuum and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With tert.-butylhydroperoxide; Cu(2+)*2CHF3O3S; palladium diacetate In decane at 64 - 65℃; for 2h; Inert atmosphere; | 1.20 General procedure: To a reaction flask dried in an oven under a nitrogen atmosphere Pd (OAc) 2 (5.6 mg, 5 mol%), Cu (OTf) 2 (45 mg, 25 mol%), 2,4-dihydroxyacrylcarbonyl (Or naphthol and 1,4-dihydroxynaphthalene) (5.0 mmol), THF (or ethers and alcohols) (5.0 mL), and t-butyl hydroperoxide (TBHP, 5.0-6.0 M in decane, 0.1 mL, 0.6 mmol).The reaction mixture was stirred on an oil bath at 65°C for 2-24 h. Subsequently, the volatiles were removed under vacuum and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With tert.-butylhydroperoxide; Cu(2+)*2CHF3O3S; palladium diacetate In decane at 64 - 65℃; for 18h; Inert atmosphere; | 1.22 General procedure: To a reaction flask dried in an oven under a nitrogen atmosphere Pd (OAc) 2 (5.6 mg, 5 mol%), Cu (OTf) 2 (45 mg, 25 mol%), 2,4-dihydroxyacrylcarbonyl (Or naphthol and 1,4-dihydroxynaphthalene) (5.0 mmol), THF (or ethers and alcohols) (5.0 mL), and t-butyl hydroperoxide (TBHP, 5.0-6.0 M in decane, 0.1 mL, 0.6 mmol).The reaction mixture was stirred on an oil bath at 65°C for 2-24 h. Subsequently, the volatiles were removed under vacuum and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With tert.-butylhydroperoxide; Cu(2+)*2CHF3O3S; palladium diacetate In decane at 65℃; for 18h; Inert atmosphere; | 1.23 General procedure: To a reaction flask dried in an oven under a nitrogen atmosphere Pd (OAc) 2 (5.6 mg, 5 mol%), Cu (OTf) 2 (45 mg, 25 mol%), 2,4-dihydroxyacrylcarbonyl (Or naphthol and 1,4-dihydroxynaphthalene) (5.0 mmol), THF (or ethers and alcohols) (5.0 mL), and t-butyl hydroperoxide (TBHP, 5.0-6.0 M in decane, 0.1 mL, 0.6 mmol).The reaction mixture was stirred on an oil bath at 65°C for 2-24 h. Subsequently, the volatiles were removed under vacuum and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With tert.-butylhydroperoxide; Cu(2+)*2CHF3O3S; palladium diacetate In decane at 64 - 65℃; for 20h; Inert atmosphere; | 1.25 General procedure: To a reaction flask dried in an oven under a nitrogen atmosphere Pd (OAc) 2 (5.6 mg, 5 mol%), Cu (OTf) 2 (45 mg, 25 mol%), 2,4-dihydroxyacrylcarbonyl (Or naphthol and 1,4-dihydroxynaphthalene) (5.0 mmol), THF (or ethers and alcohols) (5.0 mL), and t-butyl hydroperoxide (TBHP, 5.0-6.0 M in decane, 0.1 mL, 0.6 mmol).The reaction mixture was stirred on an oil bath at 65°C for 2-24 h. Subsequently, the volatiles were removed under vacuum and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With tert.-butylhydroperoxide; Cu(2+)*2CHF3O3S; palladium diacetate In benzene at 64 - 65℃; for 24h; Inert atmosphere; | 1.27 General procedure: To a reaction flask dried in an oven under a nitrogen atmosphere Pd (OAc) 2 (5.6 mg, 5 mol%), Cu (OTf) 2 (45 mg, 25 mol%), 2,4-dihydroxyacrylcarbonyl (Or naphthol and 1,4-dihydroxynaphthalene) (5.0 mmol), THF (or ethers and alcohols) (5.0 mL), and t-butyl hydroperoxide (TBHP, 5.0-6.0 M in decane, 0.1 mL, 0.6 mmol).The reaction mixture was stirred on an oil bath at 65°C for 2-24 h. Subsequently, the volatiles were removed under vacuum and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With dmap; boron trifluoride diethyl etherate In dichloromethane at -15 - 20℃; for 12.5h; Molecular sieve; Inert atmosphere; | |
2.923 g | With boron trifluoride diethyl etherate In dichloromethane at -15 - 20℃; for 16.5h; Molecular sieve; | 3.3. Synthesis of Carbohydrate-Substituted Naphthalenes 1 General procedure: In short, 1,4-Naphthoquinone 3 (5 mmol) was dissolved in EtOAc (15 mL) and anaqueous solution of sodium dithionite (2.61 g, 15 mmol, 15 mL) was added under nitrogenatmosphere at room temperature. After stirring for 3 h, the mixture was diluted with asaturated solution of ammonium chloride (15 mL) and extracted with EtOAc (3 x 25 mL).The combined organic layers were washed with water (50 mL) and brine (50 mL) anddried over magnesium sulfate. The solvent was removed in vacuo, and the crude 1,4-dihydroxynaphthalene 5 was directly used for the next step.The crude 1,4-dihydroxynapthalene 5 was dissolved in dry dichloromethane (50 mL),molecular sieves (4 Å), and a solution of trichloroacetimidate 6 (4.93 g, 10 mmol) in drydichloromethane (50 mL) was added at room temperature. The mixture was cooled to15 C, and a solution of BF3Et2O (0.13 mL, 1 mmol) in dry dichloromethane (5 mL) wasadded within 30 min. After stirring for 16 h at room temperature, the mixture was filteredover celite; washed with saturated solution of NaHCO3 (50 mL), water (50 mL), and brine(50 mL); and dried over magnesium sulfate. The solvent was removed in vacuo, and thecrude products were purified by column chromatography (hexanes/EtOAc 1:1) to obtainthe carbohydrate-substituted naphthalenes 1 in analytically pure form. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; for 4h; | General Procedure. General procedure: The following procedure is the generalized synthetic procedure used for the synthesis of 2-amino-substituted-1,4-naphthoquinone derivatives. To the mixture of 1,4-dihydroxy naphthalene (100 mg, 0.62 mmol), amine (0.75 mmol), and CeCl3*7H2O (20 mg, 0.062 mmol) in 10 mL ethanol, TEA (1.25 mmol) was added at room temperature. The reaction mixture was stirred for 4 h at room temperature. After the reaction was confirmed as completed by TLC (DCM: MeOH = 19: 1), 10 mL cold water was added to the reaction solution. The resulting precipitate was filtered and washed with 20 mL EtOH. The desired 1,4-naphthoquinone derivatives were obtained as a solid compound. 2-((4-methoxyphenyl)amino)naphthalene-1,4-dione (10): Compound 10 was obtained as a solid in 30% yield by the general procedure. 1H NMR (400 MHz, DMSO-d6) δ 3.78 (s, 3H), 5.92 (s, 1H), 7.01 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 7.77 (t, J = 7.2 Hz, 1H), 7.85 (t, J = 7.6 Hz, 1H), 7.94 (d, J = 7.6 Hz, 1H), 8.05 (d, J = 7.2 Hz, 1H), 9.15 (s, 1H). 13C NMR (DMSO-d6, 100 MHz) δ 55.8, 101.5, 115 (2C), 125, 126.1 (2C), 126.5, 130.9, 131.1, 132.9, 133.2, 135.4, 147.4, 157.4, 182.2,1825.7 ESI-MS: m/z [M + H]+ 280.1 (Calcd 279.29). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; for 4h; | General Procedure. General procedure: The following procedure is the generalized synthetic procedure used for the synthesis of 2-amino-substituted-1,4-naphthoquinone derivatives. To the mixture of 1,4-dihydroxy naphthalene (100 mg, 0.62 mmol), amine (0.75 mmol), and CeCl3*7H2O (20 mg, 0.062 mmol) in 10 mL ethanol, TEA (1.25 mmol) was added at room temperature. The reaction mixture was stirred for 4 h at room temperature. After the reaction was confirmed as completed by TLC (DCM: MeOH = 19: 1), 10 mL cold water was added to the reaction solution. The resulting precipitate was filtered and washed with 20 mL EtOH. The desired 1,4-naphthoquinone derivatives were obtained as a solid compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; for 4h; | General Procedure. General procedure: The following procedure is the generalized synthetic procedure used for the synthesis of 2-amino-substituted-1,4-naphthoquinone derivatives. To the mixture of 1,4-dihydroxy naphthalene (100 mg, 0.62 mmol), amine (0.75 mmol), and CeCl3*7H2O (20 mg, 0.062 mmol) in 10 mL ethanol, TEA (1.25 mmol) was added at room temperature. The reaction mixture was stirred for 4 h at room temperature. After the reaction was confirmed as completed by TLC (DCM: MeOH = 19: 1), 10 mL cold water was added to the reaction solution. The resulting precipitate was filtered and washed with 20 mL EtOH. The desired 1,4-naphthoquinone derivatives were obtained as a solid compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; for 4h; | General Procedure. General procedure: The following procedure is the generalized synthetic procedure used for the synthesis of 2-amino-substituted-1,4-naphthoquinone derivatives. To the mixture of 1,4-dihydroxy naphthalene (100 mg, 0.62 mmol), amine (0.75 mmol), and CeCl3*7H2O (20 mg, 0.062 mmol) in 10 mL ethanol, TEA (1.25 mmol) was added at room temperature. The reaction mixture was stirred for 4 h at room temperature. After the reaction was confirmed as completed by TLC (DCM: MeOH = 19: 1), 10 mL cold water was added to the reaction solution. The resulting precipitate was filtered and washed with 20 mL EtOH. The desired 1,4-naphthoquinone derivatives were obtained as a solid compound. |
92% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; for 6h; | 2 [Example 2] Preparation of 2-amine substituted 1,4-naphthoquinone compound 2 1,4-Dihydroxy naphthalene (100mg, 0.624mmol )was dissolved in 10mL CeCl EtOH37H2O (20mg, 0.062mmol), Di- (2-picolyl) amine (149mg, 0.7488mmol) and the TEA (130mg , 1.25mmol), and the turn was reacted at room temperature was slowly added.After 6 hours check the reaction completion (DCM: MeOH = 19: 1 confirmed by TLC), and then, the resulting solid was filtered and recrystallized with water the desired compound 2 was obtained (yield 92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With cerium(III) chloride heptahydrate; triethylamine; In ethanol; at 20℃; for 6h; | 1,4-Dihydroxy naphthalene (100mg, 0.624mmol )was dissolved in 10mL CeCl EtOH37H2O (20mg, 0.062mmol), N, N-Dibutylaminopropylamine (140mg, 0.7488mmol) and TEA (130mg, 1.25mmol) dropping to turn slowly and the reaction was carried out at room temperature.After 6 hours check the reaction completion (EA: HEX = 1: 4 check with TLC) and then, after water quenched and extracted with DCM, and anhydrous MgSO4was dried and concentrated under reduced pressure and filtered.The obtained residue was purified by silica column chromatography (developing solvent HEX -> EA: HEX = 1 :up to 6) to give the desired compound 4 was obtained (yield: 38%). |
With cerium(III) chloride heptahydrate; triethylamine; In ethanol; at 20℃; for 4h; | General procedure: The following procedure is the generalized synthetic procedure used for the synthesis of 2-amino-substituted-1,4-naphthoquinone derivatives. To the mixture of 1,4-dihydroxy naphthalene (100 mg, 0.62 mmol), amine (0.75 mmol), and CeCl3*7H2O (20 mg, 0.062 mmol) in 10 mL ethanol, TEA (1.25 mmol) was added at room temperature. The reaction mixture was stirred for 4 h at room temperature. After the reaction was confirmed as completed by TLC (DCM: MeOH = 19: 1), 10 mL cold water was added to the reaction solution. The resulting precipitate was filtered and washed with 20 mL EtOH. The desired 1,4-naphthoquinone derivatives were obtained as a solid compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With cerium(III) chloride heptahydrate; triethylamine; In ethanol; at 20℃; for 4h; | General procedure: The following procedure is the generalized synthetic procedure used for the synthesis of 2-amino-substituted-1,4-naphthoquinone derivatives. To the mixture of 1,4-dihydroxy naphthalene (100 mg, 0.62 mmol), amine (0.75 mmol), and CeCl3*7H2O (20 mg, 0.062 mmol) in 10 mL ethanol, TEA (1.25 mmol) was added at room temperature. The reaction mixture was stirred for 4 h at room temperature. After the reaction was confirmed as completed by TLC (DCM: MeOH = 19: 1), 10 mL cold water was added to the reaction solution. The resulting precipitate was filtered and washed with 20 mL EtOH. The desired 1,4-naphthoquinone derivatives were obtained as a solid compound. |
30% | With cerium(III) chloride heptahydrate; triethylamine; In ethanol; at 20℃; for 6h; | 1,4-Dihydroxy naphthalene (100mg, 0.624mmol )was dissolved in 10mL CeCl EtOH37H2O (20mg, 0.062mmol), Oleylamine (200mg, 0.7488mmol) and TEA (130mg, 1.25mmol) in turn, to slowly It was added dropwise and reacted at room temperature.After 6 hours check the reaction completion (EA: HEX = 1: 4 check with TLC) and then, after water quenched and extracted with DCM, and anhydrous MgSO4was dried and concentrated under reduced pressure and filtered.The obtained residue was purified by silica column chromatography (developing solvent HEX -> EA: HEX = 1 :up to 6) to give the desired compound 5 was obtained (yield: 30%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With cerium(III) chloride heptahydrate; triethylamine; In ethanol; at 20℃; for 4h; | General procedure: The following procedure is the generalized synthetic procedure used for the synthesis of 2-amino-substituted-1,4-naphthoquinone derivatives. To the mixture of 1,4-dihydroxy naphthalene (100 mg, 0.62 mmol), amine (0.75 mmol), and CeCl3*7H2O (20 mg, 0.062 mmol) in 10 mL ethanol, TEA (1.25 mmol) was added at room temperature. The reaction mixture was stirred for 4 h at room temperature. After the reaction was confirmed as completed by TLC (DCM: MeOH = 19: 1), 10 mL cold water was added to the reaction solution. The resulting precipitate was filtered and washed with 20 mL EtOH. The desired 1,4-naphthoquinone derivatives were obtained as a solid compound. |
18.5% | With cerium(III) chloride heptahydrate; triethylamine; In ethanol; at 20℃; for 6h; | 1,4-Dihydroxy naphthalene (200 mg, 1.248 mmol) was dissolved in EtOH (10 mL) and then CeCl3 7H2O (20 mg, 0.062 mmol), N, N- 1.25 mmol) were slowly added dropwise in this order and reacted at room temperature. After 6 hours, the reaction was confirmed to be complete (TLC with DCM: MeOH = 19: 1), followed by quenching with water and DCM, Dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The obtained residue was purified by silica column chromatography (developing solvent HEX - & gt; DCM: MeOH = 19: 1) to obtain the target compound 6 (yield: 18.5%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.3% | With aluminum oxide In 5,5-dimethyl-1,3-cyclohexadiene Reflux; | 19.a (a) Preparation of difuran core 2,5-bis(4-bromophenyl)naphtho[1,2-b:4,3- b']difuran (product 3) 1,4-Naphthalenediol (14.4 g, 0.0899 mol), 4-bromophenacyl bromide (70.02 g, 0.2519 mol), basic alumina (150 g, 1.4712 mol) and 420 mL xylenes were refluxed overnight. The slurry was hot filtered through a medium glass frit and allowed to cool. The generated solids were filtered from the cooled filtrate, washed with toluene and methanol to yield a grey solid that was triturated with THF for 1.7g of product 3.3% yield |
With aluminum oxide In toluene for 16h; Glovebox; Inert atmosphere; Reflux; | 25.a In a nitrogen filled glove box, 4-bromophenacyl-bromide (23.3mL) and 1,4-naphthalene-diol (4.8 g) were dissolved into 140mL dry toluene. 50 g basic alumina was added and the slurry stirred at reflux for 16hrs. The reaction mixture was removed from the glove box and hot filtered at 70C to remove the alumina which was washed with another 50 mL hot toluene and the resulting solution was reduced in volume to approximately 100mL. The solution was cooled and allowed to crystallize generating ~1.5 g of the desired product as confirmed by UPLC/MS and 1-H nmr. The solid was collected by filtration, washed with methanol and suction dried. Further purification was effected by extensive washing with THF and toluene followed by vacuum drying. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.4% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; for 6h; | 3 [Example 3] Preparation of 2-amine substituted 1,4-naphthoquinone compound 3 1,4-Dihydroxy naphthalene (100mg, 0.624mmol )of CeCl dissolved in 10mL EtOH37H2O (20mg, 0.062mmol), 2- (2-methyl-5-nitro-1H-imidazol-1-yl) ethanamine (196mg, 0.7488mmol) and TEA (253mg, 2.496mmol) to turn slowly added and allowed to react at room temperature.After 6 hours check the reaction completion (DCM: MeOH = 19: 1 confirmed by TLC), and then, the resulting solid was filtered and recrystallized with water the desired compound 3 was obtained (yield: 73.4%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; Further stages; | 7 [Example 7] Preparation of 2-amine substituted 1,4-naphthoquinone compound 7 After dissolving 1,4-Dihydroxy naphthalene (100 mg, 1.0 eq) in 10 mL of EtOH, CeCl3 7H2O (23 mg, 0.1 eq), N, NDimethyl-p-phenylenediamine (101.9 mg, 1.2 eq) eq) were slowly added dropwise in succession and reacted overnight at room temperature.After confirmation of the completion of the reaction (EA: HEX = 1: 1, TLC was confirmed), recrystallization with water was performed to obtain a target compound 7 (yield 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; Further stages; | 8 [Example 8] Preparation of 2-amine substituted 1,4-naphthoquinone compound 8 1,4-Dihydroxy naphthalene (100 mg, 0.624 mmol) was dissolved in EtOH (10 mL), and CeCl3 7H2O (20 mg, 0.062 mmol), 2-Thiopheneethylamine (95 mg, 0.7488 mmol) and TEA And then reacted at room temperature. After confirmation of the completion of the reaction (EA: HEX = 1: 3, TLC was confirmed), recrystallization with water was performed to obtain a target compound 8 (yield 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; | 9 1,4-Dihydroxy naphthalene (100 mg, 0.624 mmol) was dissolved in 10 mL of EtOH followed by CeCl3 7H2O (20 mg, 0.062 mmol), prop-2-yn-1-amine (41 mg, 0.7488 mmol) mmol) were slowly added dropwise in this order and reacted at room temperature. After confirming the completion of the reaction (EA: HEX = 1: 3, TLC was confirmed), recrystallization with water was conducted to filter the resulting solid to obtain Compound 9A (yield: 70%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With cerium(III) chloride heptahydrate; triethylamine In ethanol at 20℃; for 6h; | 1 [Example 1] Preparation of 2-amine substituted 1,4-naphthoquinone compound 1 1,4-Dihydroxy naphthalene (100mg, 0.624mmol )was dissolved in 10mL CeCl EtOH37H2O (20mg, 0.062mmol), Tryptamine (120mg, 0.7488mmol) and TEA (130mg, 1.25mmol) in turn, to slowly It was added dropwise and reacted at room temperature.After 6 hours check the reaction completion (DCM: MeOH = 19: 1, confirmed by TLC), and then, the resulting solid was filtered and recrystallized with water the desired compound 1 (yield: 82%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: 4-(1H-imidazo[4,5-b]pyridin-2-yl)aniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: 1,4-Dihydroxynaphthalene With sodium hydroxide In water at 0 - 5℃; for 2h; | 6 4.1.6. General procedure for preparation of substituted 1-{4-(1H-imidazo[4,5-b]pyridin-2-yl)phenyl}diazene (Azocoupling products) VIIa-f General procedure: A solution of sodium nitrite (0.89 g, 0.013 mol) in distilled water (5ml) was added portion wise to a stirred ice-cooled solution of compoundI (2.10 g, 0.01 mol) in HCl (2.5 ml) and distilled water (5 ml).The cold diazonium solution was added portion wise to a solution of theappropriate phenolic compound (0.01 mol) in an aqueous solution of10% sodium hydroxide (4 ml) while stirring and cooling. The reactionmixture was kept in ice for 2 h, then filtered and dried. The crudeproduct was crystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium hydroxide In tetrahydrofuran at 65℃; for 12h; Inert atmosphere; | 3.1 Embodiment 3 step 1:Under the protection of nitrogen atmosphere,Weigh 2-chloromethylindole-1-aldehyde (2.39g, 10.00mmol),1,4-naphthalene diphenol (1.60 g, 10.00 mmol) and potassium hydroxide (1.68 g, 30.00 mmol)Dissolved in a round bottom flask containing 50 mL of tetrahydrofuran.The reaction was stirred at 65 ° C for 12 hours.SaidThe ratio of the substances of 2-dichloromethylindol-1-aldehyde and 1,4-naphthalenediol is 1:1.After the reaction is over,Spin the reaction solution,Recrystallization from methanol, filtration, drying, weighing, yield 77%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With potassium hydroxide In tetrahydrofuran at 65℃; for 12h; Inert atmosphere; | 3.2 Step 2 is the same as step 1,Just will2-dichloromethylguanidin-1-acetalChange toTerephthalaldehyde:Protected in a nitrogen atmosphereProtectionunder,Weighed the dialdehyde (1.84g, 10.00mmol),1,4-naphthalenediol (1.60g, 10.00mmol)And potassium hydroxide (1.68g, 30.00mmol)Dissolved in a round bottom flask containing 50 mL of tetrahydrofuran.The reaction was stirred at 65 ° C for 12 hours.The amount ratio of the substances of the terpene dialdehyde and the 1,4-naphthalenediol is 1:1.After the reaction is over,Spin the reaction solution,Recrystallization from methanol,filter,dry,Weighing,The yield was 51%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With tert.-butylhydroperoxide; copper(II) bis(trifluoromethanesulfonate) at 80℃; for 7h; | 1 Synthesis Example 1 Synthesis of Compound 4, 8-29 General procedure: General procedures for the synthesis of various derivatives, including anthracene-1,4-dione, 1,4-benzoquinone, Naphthalene-1,4-diol, dihydroxyanthracene-9,10-dione, substituted or unsubstituted 1,4-naphthoquinone (6; Cu (OTf) 2 (5 mol%) was added to the solvent of cycloalkane (7; 10.0 mmol), and then 3 equivalents of TBHP were added using a syringe.Then, the reaction was carried out by raising the temperature to 80 ° C for 6-7 hours or refluxing at atmospheric pressure. To obtain the residue, the solvent was evaporated in a rotary evaporator under reduced pressure, and the residue was then purified by silica gel flash column chromatography to give the desired product (4, 9-29). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium hydroxide In tetrahydrofuran; water for 4h; Reflux; | 2 Synthesis of intermediate LA: Dissolving 1,4-dihydroxynaphthalene (1 eq) in tetrahydrofuran,Dissolve KOH (8 eq) in a small amount of water.And added to the reaction solution,Add TsOCH2CH2Cl (4 eq),The reaction solution was heated to reflux for 4 hours;Cool to room temperature,Extracted with CH2Cl2,Combine the organic phase,Dry with anhydrous Na2SO4,Then evaporated to dryness on a rotary evaporator to give a yellow solid.The crude product is purified by recrystallization (petroleum ether:The volume ratio of dichloromethane is 3:2);Get a yellow needle,The yield is 90%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
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26% | With methanesulfonic acid at 85℃; for 4h; Inert atmosphere; | 4.1.2. General procedure for the preparation of compounds 24-25 General procedure: Hydroquinone (22-23, 14.7 mmol) was mixed with 3,3-dimethylacrylic acid methyl ester (1.9 g, 16.2 mmol) and methanesulfonic acid (50 mL). The mixture was stirred at 85° Cunder nitrogen for 4 h and then cooled to room temperature. To themixture was added 100 g of ice with stirring. The reaction mixturewas extracted with EtOAc (3 x 100 mL). The combined organic layerwas washed with saturated NaHCO3 (3 x 100 mL) and water(3 x 100 mL) and dried over Na2SO4. After filtration and evaporation,the crude product (24-25) was obtained which was purifiedthrough column chromatography over silica gel. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With ammonium peroxydisulfate; iodine; iron In 1,2-dichloro-ethane at 120℃; for 24h; Sealed tube; | |
81% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With ammonium peroxydisulfate; iodine; iron In 1,2-dichloro-ethane at 120℃; for 24h; Sealed tube; | |
76% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With ammonium peroxydisulfate In 1,2-dichloro-ethane at 80℃; for 2h; Green chemistry; | General procedures for the synthesis of 3-indolylquinones General procedure: To a solution of DCE (2 mL) was added 1 or 4a (0.4 mmol), 2 (0.8 mmol) and(NH4)2S2O8 (2 equiv). The mixture was stirred at 80 °C (temperature of the oil bath) for about 2 h under air atmosphere. After the completion of the reaction (monitored byTLC), and cooled down to room temperature, the reaction was quenched with brine (5ml) and the mixture was extracted with EtOAc (3 × 5 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed in vacuo.The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3. |
Yield | Reaction Conditions | Operation in experiment |
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85% | With phosphoric acid In water monomer at 100℃; for 8h; Inert atmosphere; Schlenk technique; Green chemistry; | 10 Example 10 32.01 mg (0.2 mmol) 1,4-dihydroxynaphthalene, 58.8 mg (0.2 mmol) 4-phenylmethylene-2,6-di-tert-butyl-2,5-cyclohexadien-1-one , (0.01 mmol) phosphoric acid and 1.0 mL of water were added to a Schlenk tube under nitrogen atmosphere, and the reaction was stirred at 100 oC for 8 hours. After the reaction was completed, the yield of the target product was 85% after separation and purification by column chromatography. |
Tags: 571-60-8 synthesis path| 571-60-8 SDS| 571-60-8 COA| 571-60-8 purity| 571-60-8 application| 571-60-8 NMR| 571-60-8 COA| 571-60-8 structure
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Code | Phrase |
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Code | Phrase |
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P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
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P378 | |
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P370 + P378 | In case of fire: |
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P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
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Storage | |
Code | Phrase |
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Disposal | |
Code | Phrase |
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Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
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H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
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H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
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H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
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H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
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H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
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H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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