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CAS No. : | 15804-19-0 | MDL No. : | MFCD00006723 |
Formula : | C8H6N2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ABJFBJGGLJVMAQ-UHFFFAOYSA-N |
M.W : | 162.15 | Pubchem ID : | 27491 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 45.19 |
TPSA : | 65.72 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.15 cm/s |
Log Po/w (iLOGP) : | 0.75 |
Log Po/w (XLOGP3) : | 0.2 |
Log Po/w (WLOGP) : | 0.22 |
Log Po/w (MLOGP) : | 0.6 |
Log Po/w (SILICOS-IT) : | 2.22 |
Consensus Log Po/w : | 0.8 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.59 |
Solubility : | 4.19 mg/ml ; 0.0258 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.14 |
Solubility : | 11.8 mg/ml ; 0.0726 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -3.13 |
Solubility : | 0.12 mg/ml ; 0.000738 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.78 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
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 |
---|---|---|
93% | Stage #1: With trichlorophosphate In N,N-dimethyl-formamide at 50℃; for 4 h; Stage #2: With ammonia In waterCooling with ice |
General procerure: A mixture of quinoxalin-2,3(1H,4H)-dione (1) [16] or compound 2 (40 mmol) and phosphours oxychloride (100 mmol) in dimethyl foramide (20 mL) was stirred at 50 °C for 4 h. The reaction mixture was added portion wise to ice/water and neutralized with ammonia solution 30percent. The formed precipitate was filtered off and purified on column chromatography by using petroleum ether (60-80): ethyl acetate (9:1) as an eluent. |
80% | for 5 h; Reflux | A solution of compound 7 (30.84mmol, 5.0g) in phosphorus oxychloride (30mL) was reacted under refluxing condition for 5h, then the reaction was totally quenched by slowly pouring into cooled ammonia solution. The mixture was extracted with ethyl acetate (2×50mL), the combined organic phase was washed with brine (30mL) and dried over anhydrous MgSO4. After evaporated in vacuo, the crude residue was purified by silica gel flash chromatography (PE/EtOAc=10:1, v:v) to give 4.9g of corresponding product with 80percent yield. M.p. 149–150°C; ESI-MS m/z: 199.8 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | at 79 - 100℃; for 1 h; | General procedure: N,N-Dimethylformamide (0.5 mg, 0.0673 mmol) was added dropwise to a slurry of 2,3-dihydroxyquinoxaline (2.0 g,12.3 mmol) and thionyl chloride (2.92 g, 24.6 mmol) in1-chlorobutane (20 mL). The mixture was refluxed for 1h.Then cooled to ambient temperature, the obtained needles were filtered, washed with ethyl ether, and dried.2,3-Dichloroquinoxaline (2a): white needles, yield 98percent; mp100–102 °C(lit. 16 m.p. 100–102 °C); FT-IR (KBr, cm-1):3049, 1618, 1562,753; 1H NMR (350 MHz, CDCl3): δ 8.07–8.02 (m, 2H, ArH), 7.85–7.80 (m, 2H, ArH); 13C NMR(CDCl3): 143.3, 140.9, 131.6, 127.8. Anal. Calcd. forC8H4Cl2N2: C, 48.28; H, 2.03; N, 14.07. Found: C, 47.52; H,1.89; N, 14.15. |
96% | With thionyl chloride; N,N-dimethyl-formamide In 1,2-dichloro-ethane for 2 h; Reflux | 31 mlof 1,2-dichloroethane in 3.5ml (48.1 mmol) of thionyl chloride and 3.0g (18.5mmol) of 2,3-dihydroxy quinoxaline in the slurry after the saline is slowlycatalytic amounts of dimethylformamide do. The reaction mixture was refluxedfor 2 hours. After the reaction was complete and then concentrated completelydissolved into the 35 ml of 1,2- dichloroethane it gives back again tocompletely concentrated. When the solid product thus obtained wasrecrystallized using acetonitrile and distilled water to obtain a solid whiteneedle-like crystals of 3.5 g (96percent yield). |
95% | With thionyl chloride In 1,2-dichloro-ethane; N,N-dimethyl-formamide for 2 h; Reflux | DMF (0.045 g, 0.00062 mol) was added dropwise to a slurry of 2,3-dihydroxyquinoxaline (2, 2.0 g,0.012 mol) and thionyl chloride (3.7 g, 0.031 mol) in 1,2-dichloroethane (20 mL). The resulting reactionmixture was heated to reflux for 2 h then concentrated to dryness. The residue was dissolved in1,2-dichloroethane (25 mL) and concentrated to dryness. The resulting solid was crystallized fromCH3CN/H2O, giving 2.3 g (95percent) of 3 as fine, off-white needles. m.p. 148–150 °C [55]. |
98% | With thionyl chloride In N,N-dimethyl-formamide | Comparative Example 2 Synthesis of 2,3-Dichloroquinoxaline 2,3-Dihydroxyquinoxaline (100.0 grams, 616.7 mmoles), thionyl chloride (350 mL) and dry DMF (5 mL) were added to a 500 mL flask. The flask was connected to a condenser, which was connected to a dry column. The mixture was gradually heated at reflux until the solid had completely dissolved, which took around 6 h. Then excess thionyl chloride was removed under reduced pressure to yield 120.8 g (98percent) of crude 2,3-dichloroquinoxaline. Recrystallizations from toluene gave 86.5 g (72percent) of white needles: mp 151-152° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With water; bis-[(trifluoroacetoxy)iodo]benzene In acetonitrile at 20℃; for 24h; | |
With ammonium peroxydisulfate; water | ||
With dihydrogen peroxide; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With ammonium peroxodisulphate In lithium hydroxide monohydrate; acetonitrile at 60℃; | 1 Example 1 In a 25 mL tube, add compound 1 0.2 mmol, ammonium persulfate 0.6 mmol, add acetonitrile: water (4:1 volume ratio) 2 ml as a solvent, stirred at 60 degrees Celsius. After the TLC (Thin Layer Chromatography) detection reaction is completed, the reaction liquid is cooled to room temperature, 10 ml of water is added, filtered with a sand core funnel, and the vacuum drying box is dried to obtain the target product - Compound 2, with a yield of 91%. |
91% | With ammonium peroxodisulphate; lithium hydroxide monohydrate In acetonitrile at 60℃; | 21 Example 21 In a 25 mL test tube, add quinoxaline-2-one 0.2 mmol, ammonium persulfate 0.6 mmol, add acetonitrile: water (4:1 volume ratio) 2 ml as a solvent, stirred at 60 degrees Celsius. After the TLC (Thin Layer Chromatography) detection reaction is completed, the reaction liquid is cooled to room temperature, 10 ml of water is added, filtered with a sand core funnel, and the vacuum drying box is dried to obtain the target product, with a yield of 91%. |
75% | With tert.-butylnitrite; lithium hydroxide monohydrate In dimethyl sulfoxide at 100℃; for 3h; Sealed tube; |
52% | With sodium hydroxide; potassium permanganate In lithium hydroxide monohydrate Heating; | |
52% | With sodium hydroxide; potassium permanganate for 1h; Heating; | |
With dihydrogen peroxide; glacial acetic acid | ||
Multi-step reaction with 2 steps 1: PCl5 / 30 h / 220 - 240 °C 2: H2O / 7 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In diethylene glycol at 245℃; for 2.5h; | |
With ethylene glycol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With thionyl chloride; In dichloromethane; N,N-dimethyl-formamide; | 8.1 g (50 mmol) of quinoxaline-2,3(1H,4H)-dione, 11.9 g (100 mmol) of thionyl chloride, 5 mL of DMF was added to a round bottom flask containing 50 mL of dichloromethane.The mixture was heated to reflux and stirred until the material was removed by TLC.The reaction solution was cooled to room temperature and carefully poured into ice water.After the ice water is completely melted,Extracted in 4 portions with 200 mL of dichloromethane.Combine the organic phases.Wash the organic phase 3 to 4 times with K2CO3 solution (neutralize the residual acid),Dry over anhydrous magnesium sulfate, and remove the solvent under reduced pressure.Column chromatography gave 2,3-dichloroquinoxaline (colorless crystals, yield 94%, 9.3 g): |
93% | General procerure: A mixture of quinoxalin-2,3(1H,4H)-dione (1) [16] or compound 2 (40 mmol) and phosphours oxychloride (100 mmol) in dimethyl foramide (20 mL) was stirred at 50 C for 4 h. The reaction mixture was added portion wise to ice/water and neutralized with ammonia solution 30%. The formed precipitate was filtered off and purified on column chromatography by using petroleum ether (60-80): ethyl acetate (9:1) as an eluent. | |
93% | With thionyl chloride; N,N-dimethyl-formamide; In dichloromethane; at 45℃; for 3h; | Weigh 4.054 g of quinoxaline-2,3(1H,4H)-dione, a mixture of 3.63 ml of SOCl2 was added and added to a 250 mL flask, and 3 mL of DMF and 30 mL of CH2Cl2 were separately weighed and dissolved. The mixture was heated to 45 C, stirred for 3 h, and it was judged by TLC that the quinoxaline-2,3(1H,4H)-dione disappeared and the reaction was stopped. After the reaction solution is cooled to normal temperature, it is poured into ice water and stirred for cooling. After the ice is completely melted, it is extracted with CH2Cl2 multiple times until the upper aqueous phase is colorless and the organic phase is combined.Washed with a saturated K2CO3 solution to neutralize the residual acid, After drying with anhydrous MgSO4, suction filtration through a vacuum pump and drying under reduced pressure. Purification by column chromatography (elution of petroleum ether and ethyl acetate in a ratio of 5:1) to give the compound 2,3-dichloroquinoxaline (Colorless crystal, yield 4.629g, yield 93%): |
82% | With thionyl chloride; In 1,2-dichloro-ethane; N,N-dimethyl-formamide; for 4h;Heating; | A mixture of <strong>[15804-19-0]quinoxaline-2,3-dione</strong> (3.08 g, 0.019 mol) in 1,2-dichloroethane (25 mL)and thionyl chloride (4 mL, 0.055 mol) dissolved in few drops of dimethylformamide was heatedon water bath for 4 h. The reaction mixture was then cooled to room temperature and the resultingprecipitate was isolated by filtration, washed with water, then crystalized from rectified spirit ascolorless crystals, 82% yield; m.p. 143-145 C. 1H-NMR (500 MHz: CDCl3), delta 8.01 (dd, 2H, J = 6.4,3.5 Hz, H6 and H7) and 7.79 (dd, 2H, J = 6.4, 3.4 Hz, H5 and H8) ppm. |
81% | With trichlorophosphate; In N,N-dimethyl-formamide; at 90℃;Inert atmosphere; | POCl3 (75 mL, 800 mmol) was slowly added to a two-neck, 250 mL flask with 2a (16.20 g, 100 mmol) under N2, followed by DMF (15 mL, 200 mmol). The resultant solution was heated to reflux (90 C) with vigorous stirring for 8 h. After completion, the reaction was cooled to room temperature and poured into ice water. The solid obtained was filtered, washed with water and recrystallized from CH2Cl2 to give 3a as white solid (16.13 g, 81 %). M. P.: 149.2-150.4 C. 1H NMR (400 MHz, DMSO) delta 8.09 (dd, J = 6.3, 3.5 Hz, 2H), 7.95 (dd, J = 6.4, 3.4 Hz, 2H). |
80% | With trichlorophosphate; for 5h;Reflux; | A solution of compound 7 (30.84mmol, 5.0g) in phosphorus oxychloride (30mL) was reacted under refluxing condition for 5h, then the reaction was totally quenched by slowly pouring into cooled ammonia solution. The mixture was extracted with ethyl acetate (2×50mL), the combined organic phase was washed with brine (30mL) and dried over anhydrous MgSO4. After evaporated in vacuo, the crude residue was purified by silica gel flash chromatography (PE/EtOAc=10:1, v:v) to give 4.9g of corresponding product with 80% yield. M.p. 149-150C; ESI-MS m/z: 199.8 [M+H]+. |
With N,N-dimethyl-formamide; trichlorophosphate; at 50℃; for 5h; | Take 2.0mmol compound obtained in step II, isdissolved in 5.0mmol DMF was added 5.0mmol POCl3, 50 C the reaction was stirred for 5h (TLCdetection). After completion of the reaction, the reaction solution was poured into 200ml of ice water, theproduct gradually precipitated in the solid form to the entire bottom, filtered, and washed three times with coldethanol (approximately in 3 ml of each), with a mixture of acetone and ethanol (volume ratio of ethanol: acetone= 10/1) and recrystallized to give the title compound. | |
With N,N-dimethyl-aniline; trichlorophosphate; at 100 - 105℃; | General procedure: Method B. To a cold solution of heterocyclic amide (2.5 mmol)in POCl3 (25 mL) was added dimethylaniline (2.5 mmol). Thereaction mixture was stirred under reflux (100-105 C) for1.5-2 h. The excess POCl3 was removed under reduced pressure. The residue was poured into a mixture of chloroform(50 mL), ice water (80 mL) and ammonia (5 mL). The chloroform layer was separated, dried over Na2SO4 and filtered. Tothis chloroform solution of the in situ generated chloroheterocycles was added (0.69 g, 2.5 mmol) of N-cyclohexyl dithiocarbamate cyclohexylammonium salt. The reaction mixture was refluxed at 61 C for 12 h. The reaction mixture was evaporatedunder reduced pressure and 25 mL of ethanol was added to thesolid residue. The yellowish-orange precipitate was filtered togive the desired product. The crude compounds were pureenough for analytical purposes. Purification of products foranalysis was achieved by crystallization from the appropriatesolvent; chromatographed with the appropriate eluent or byrepeated dissolution in KOH and reprecipitation by acetic acid. | |
With trichlorophosphate; at 120℃; for 5h; | 5.0 g of quinoxaline-2,3(1H,4H)-dione obtained in the step (1) is dissolved in phosphorus oxychloride (or thionyl chloride), and refluxed at 120 C for 5 hours.The reaction mixture was poured into glacial ammonia water to quench the reaction. After quenching, the aqueous phase was extracted twice with ethyl acetate.The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1, v: v). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With trichlorophosphate; In dichloromethane; at 20℃; for 12h; | A mixture of quinoxalin-2,3(1H,4H)-dione (1) [16] (40 mmol) and phosphorus oxychloride (60 mmol) in methylene chloride (50 mL) was stirred at room temperature for 12 h. The excess solvent was evaporated under reduced pressure. The residue was dissolved in ice/water and neutralized with ammonia solution 30%. The formed precipitate was filtered off and purified on column chromatography by using petroleum ether (60-80): ethyl acetate (7:3) as an eluent. Crystal structure of compound 3 obtained. |
With thionyl chloride; In N,N-dimethyl-formamide; toluene; at 130℃; for 2h; | The quinoxalin-2-one of the present example is prepared with phenyl-1,2-diamine and oxalic acid via the method described in Example 12 to afford the 1,4-Dihydro quinoaxline-2,3-dione. The 1,4-Dihydro quinoaxline-2,3-dione is then treated with SOCl2 in 2.5% DMF:toluene, heated to 130 C., stirred for 2 h, filtered and concentrated to afford the 3-chloro-1H-quinoxalin-2-one in crude form. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With Lawessons reagent In toluene for 4h; Heating; | |
With pyridine; tetraphosphorus decasulfide | ||
With tetraphosphorus decasulfide; xylene |
Multi-step reaction with 2 steps 1: trichlorophosphate; <i>N</i>,<i>N</i>-dimethyl-aniline / 100 - 105 °C 2: cyclohexylaminodithiocarboxylic acid, cyclohexylammonium salt / chloroform / 12 h / 61 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrazine hydrate; In ethanol; at 20℃; for 3h; | General procerure: A mixture of compound 1, 2 or 4 (7 mmol), ethanol (50 mL) and hydrazine monohydrate 98% (10 mL) was stirred at room temp. for 3 h, 0.5 h, or 5 h, respectively, according to the starting agent. The reaction mixture was evaporated under reduced pressure. The solid residue was washed with ethanol and recrystallized from dimethylformamide as a yellowish white powder. Rf = 0.39 (petroleum ether/ethyl acetate/methanol, 1: 1: 0.25). Yield: 60-80%, m.p. > 300 C (lit. > 360 C [21]). 1H NMR (500 MHz, DMSO-d6): 4.52(br., 2H, NH2, D2O exchangeable), 7.11(m, 1H), 7.27(m, 1H); 7.34(m, 1H), 7.6(m, 1H); 8.75(br., NH, D2O exchangeable), 12.17(br., NH, D2O exchangeable). 13C NMR (500 MHz, DMSO-d6): 115.91, 123.89, 125.98, 129.11, 131.66, 142.65, 153.5, 159.23. IR (cm-1): 3404 (NH quinoxaline), 3332-3200 (NHNH2), 3050, 2968 (CH, aromatic), 1680 (CO), 1615 (CN), 1580, 1500 (CC). MS: [m/z (rel.abundance)]: 176(M+, 55%). Anal. Calcd for C8H8N4O (FW: 176.07): C, 54.54; H, 4.58; N, 31.80. Found: C, 54.51; H, 4.65; N, 31.71. | |
With hydrazine hydrate; at 100℃; for 2h; | A solution of Synthesis of quinoxaline-2,3(1H,4H)-dione (5.0 g, 46 mmol) in hydrazine hydrate (40 mL) was stirred heated at 100 C for 2 h. After the reaction completed, cooling the mixture to room temperature, filtered and washed with water to produce a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In ethanol; for 0.1h;Microwave irradiation; | In a typical reaction, o-phenyldiamine (10mmol) and the corresponding dicarbonylic compound (10mmol) were dissolved in ethanol (5ml) in a reaction glass tube equipped with a screw cap and magnetic agitation. The reaction mixture was irradiated with microwaves (Anton Parr Monowave 300 reactor) at 30W for around 5-13min. After cooling, 10ml of ethanol was added to the reaction vessel. The product was recrystallized from ethanol, precipitating as a white solid.4.3.4.1 3-Methylquinoxalin-2(1H)-one(17) (0066) Dicarbonyl compound: pyruvic acid. Reaction time: 8.5min. Yield: 98%. Mp: 243-245. IR (cm-1): 3045, 1670, 1640. MS (m/z): 160.2. 1H-RMN (300MHz) delta (ppm) (DMSO-d6): 2,39 (s; 3H; CH3); 7.22-7.35 (sa; 2H; ArH); 7.41-7.54 (sa; 1H; ArH); 7.64-7.74 (sa; 1H; ArH); 12,33 (sa; 1H; NH). 13C-RMN (75MHz) delta (ppm) (CDCl3): 21.0 (CH3); 115.7; 123.5; 128.3; 129.8; 132.1; 132,3; 155.4 (C=N); 159.9 (C=N). |
96% | With hydrogenchloride; In water; for 6h;Heating; | 10.8 g (100 mmol) of o-phenylenediamine,13.5g (150mmol) of oxalic acid was placed in a round bottom flask,Add 100 mL of water and 10 mL of concentrated hydrochloric acid.Heat and stir for 6 hours.After returning to room temperature,Filter the reaction solution,Washed repeatedly, dried,Resulting quinoxaline -2,3 (1H, 4H) - dione (colorless crystals, yield 96%, 15.6g): |
92% | With hydrogenchloride; In water; for 8h;Reflux; | A round-bottom flask charged with benzene-1,2-diamine (46.3mmol, 5.0g) and oxalic acid (64.4mmol, 5.8g), and 250mL of distilled water was added in one portion. Then 4.5mL of concentrated hydrochloric acid was added to the suspension dropwise and the reaction mixture was refluxed for 8h. Collected the obtained brown precipitate and washed with distilled water to afford 6.9g of desired product, yield: 92%. M.p. 241-242.7C; ESI-MS m/z: 161.0 [M+H]+. |
92% | With hydrogenchloride; In water; at 100℃; for 6h; | 4.475 g of o-phenylenediamine and 6.752 g of oxalic acid were added to a 250 mL flask and mixed. Add 50 mL of water to dissolve it, add 5 mL of concentrated hydrochloric acid, and heat to 100 C. After stirring for 6 hours, it was judged by thin layer chromatography (TLC monitoring) that the starting material o-phenylenediamine disappeared and the reaction was stopped. After the reaction solution is cooled to normal temperature, vacuum pumping, washing the filtrate with water until the pH is neutral. Dry with anhydrous MgSO4 and filter again. The compound quinoxaline-2,3(1H,4H)-dione was obtained (white crystal, yield 7.476g, yield 92%) |
90% | In ethanol; for 0.116667h;Microwave irradiation; | To a solution of 1.1g (10 mmoles) of o-fenilendiamina in ethanol (5 mL) in a microwave reaction tube was oxalic acid (1g; 11.11 mmol). The reaction mixture was irradiated with MW during 1 min. at 30 W followed by 6 min at 15 W. The crude product was filtered, washed with NaOH 5% and water. Compound 7 was obtained as a white solid (1.50g, 90%) crystallized from ethanol; mp: > 320 C C; mp lit.: 410 C [2]. IR (Film): 3043, 1681, 1613, 1500 cm-1.1H-NMR (300 MHz, DMSO-d6): 7.02-7.20 (m; 4H; ArH); 11.93 (bs; 2H; OH) ppm. 13C-NMR (75 MHz, DMSO-d6): delta 115.6; 123.5; 126.0; 155.7 (C=N) ppm. MS (m/z): 162.1. |
86% | With hydrogenchloride; In water; for 4h;Reflux; | o-Phenylenediamine (27.9 g, 0.25 mol), oxalic acid (32.5 g, 0.36 mol), and 4 N HCl (150 mL) wererefluxed for 4 h then cooled. The solid separated was filtered, washed, and used without furtherpurification, yield (86%), m.p. > 300 C [lit. > 300 C] [43], 1H-NMR (500 MHz, DMSO-d6, 300 K), delta 11.91 (s, 2H, 2 NH, D2O exchangeable), 7.11 (dd, 2H, J = 6.1, 3.3 Hz, H6 and H7) and 7.07 (dd, 2H,J = 6.0, 3.3 Hz, H5 and H8) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In water at 60℃; for 2h; | |
89% | With ytterbium triflare at 80℃; for 1h; | |
89% | for 4h; Reflux; |
72% | With hydrogenchloride In water for 6h; Reflux; | |
61.3% | With pyridine for 72h; Reflux; Inert atmosphere; | |
54% | With toluene-4-sulfonic acid at 130℃; for 0.05h; microwave irradiation; | |
40% | at 50 - 80℃; | |
With hydrogenchloride In water Reflux; | ||
Reflux; | ||
at 100℃; for 12h; | 2.1. Synthesis of Quinoxaline-2,3(1H,4H)-dione (2) A solution of 1,2-phenylenediamine (1) (5.0 g, 46 mmol) in diethyl oxalate (10.1 g, 69 mmol) was in a round bottomed flask and the mixture was stirred and heated to 100 °C for 12 h. After the reaction completed, cooling the mixture to room temperature, filtered and washed with hot water and petroleum ether to obtain a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In benzene for 72h; Irradiation; | |
87.9% | In ethanol for 504h; light; | |
Multi-step reaction with 2 steps 1: 74.5 percent / ethanol / 336 h / light 2: ethanol / light |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With peracetic acid In water at 50℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With dihydrogen peroxide In acetic acid for 3h; Heating; | |
Multi-step reaction with 2 steps 1: POCl3 / dimethylformamide / 2 h / Heating 2: 63 percent / 30percent H2O2 / acetic acid / 3 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With dihydrogen peroxide In acetic acid for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In 1,4-dioxane at 50℃; for 5h; | 16 Synthesis of compound A26: Compound A4 (1.08g, 10mmol), oxalyl chloride (1.25g, 10mmol), 100ml of 1,4-dioxane were stirred at 50°C for 5 hours, the reaction product was cooled to room temperature, and the precipitate formed was filtered under reduced pressure Anhydrous magnesium sulfate was added to it to remove the water, then the solvent was removed under reduced pressure, the residue was passed through a silica gel column with dichloromethane as the eluent to obtain the product, and then the solvent was removed under reduced pressure and vacuum The product was dried to prepare the desired solid compound A26 (1.10 g, 68%), |
In various solvent(s) at 130℃; for 1h; | ||
at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With peracetic acid In water at 50℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium hydroxide; potassium permanganate In water Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With N-chloro-succinimide In N,N-dimethyl-formamide for 120h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With N-Bromosuccinimide In N,N-dimethyl-formamide for 120h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With chlorosulfonic acid at 110℃; for 8h; | |
88% | With chlorosulphone | |
78% | With chlorosulfonic acid at 0 - 60℃; |
78% | With chlorosulfonic acid at 0 - 20℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With phosphorus pentabromide In toluene at 160℃; for 3h; Inert atmosphere; | |
With phosphorus pentabromide | ||
With phosphorus pentabromide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With ytterbium triflare at 80℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With ytterbium triflare at 80℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 30 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 3 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 4 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 2 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 25 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 3 h / 120 °C |
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 5 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 4 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 10 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 0.3 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 40 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 3 h / 120 °C | ||
Multi-step reaction with 3 steps 1: trichlorophosphate / 6 h / Reflux 2: triethylamine; copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) / ethanol / 4 h / 60 °C 3: triethylamine; methanesulfonamide; copper diacetate / N,N-dimethyl-formamide / 4 h / 110 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 65 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 18 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 4 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 65 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 92 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 25 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 2 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 92 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 20 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 2 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 96 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 10 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 15 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 96 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 14 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 15 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 96 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 27 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 15 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 92 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 66 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 8 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 70 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 2 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 40 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 3 h / 100 °C | ||
Multi-step reaction with 5 steps 1: PBr5 2: 83 percent / NH4OH; K2CO3 / dimethylsulfoxide; acetonitrile / 120 h / 50 °C 3: 85 percent / CuI; Et2NH / PdCl2(PPh3)2 / dimethylformamide / 40 °C 4: triethylamine / tetrahydrofuran / 20 °C 5: 48 percent / K2CO3 / Pd(PPh3)4 / acetonitrile / 3 h / 120 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: POCl3 2: hydrazine hydrate / 20 °C | ||
Multi-step reaction with 2 steps 1: POCl3 / dimethylformamide 2: 92.5 percent / hydrazine hydrate; triethylamine / methanol / 3 h / 20 °C | ||
Multi-step reaction with 2 steps 1: 90 percent / POCl3 / dimethylformamide / 1.5 h / Heating 2: 1.2 g / KHCO3, PEG 4000, hydrazine hydrate / tetrahydrofuran; methanol / 2 h / 20 - 25 °C |
Multi-step reaction with 2 steps 1: trichlorophosphate / N,N-dimethyl-formamide / 2 h 2: hydrazine hydrate monohydrate / ethanol / 16 h / Reflux | ||
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride 2: hydrazine hydrate monohydrate / methanol / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride / 1,2-dichloro-ethane 2: hydrazine hydrate monohydrate / ethanol / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / Reflux 2: hydrazine / ethanol; lithium hydroxide monohydrate / Reflux | ||
Multi-step reaction with 2 steps 1: thionyl chloride / 1,2-dichloro-ethane; N,N-dimethyl-formamide / 4 h / Heating 2: hydrazine monohydrate / ethanol / 24 h | ||
Multi-step reaction with 2 steps 1: thionyl chloride; N,N-dimethyl-formamide / 1,2-dichloro-ethane / 2 h / Reflux 2: hydrazine monohydrate / ethanol / 16 h / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride / N,N-dimethyl-formamide; 1,2-dichloro-ethane / 2 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 4 h / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride; N,N-dimethyl-formamide / 1,2-dichloro-ethane / 2 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 16 h | ||
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride / 1,2-dichloro-ethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride / 1,2-dichloro-ethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride / N,N-dimethyl-formamide; 1,2-dichloro-ethane / 2 h / Heating 2: hydrazine monohydrate; triethylamine / ethanol / 4 h / 20 °C | ||
Multi-step reaction with 2 steps 1: thionyl chloride / 1,2-dichloro-ethane / 5 h 2: hydrazine monohydrate; triethylamine / ethanol / 4 h / 20 °C | ||
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide; thionyl chloride / 1,2-dichloro-ethane / 2 h / Reflux 2: hydrazine / ethanol / 4 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: SOCl2 / toluene; dimethylformamide / 2 h / 130 °C 2: acetonitrile / 2 h / 120 °C 3: various solvent(s) / 0.42 h / 220 - 230 °C | ||
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol 2: N,N-dimethyl-formamide / 8 h / 90 °C | ||
Multi-step reaction with 3 steps 1: trichlorophosphate / dichloromethane / 4 h / 20 °C 2: hydrazine hydrate / ethanol 3: N,N-dimethyl-formamide / 8 h / 90 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With N-Bromosuccinimide In ethanol; N,N-dimethyl-formamide | 32 Preparation of 6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione 6,7-Dibromo-1,4-dihydroquinoxaline-2,3-dione (Method B): The procedure of Mitchell, R. H. et al., J. Org. Chem. 44(25):4733 (1979) was adapted. To a stirred suspension of 1,4-dihydro-2,3-quinoxalinedione (3.24 g, 20.00 mMol, Aldrich) in dried DMF (100 mL) was added N-bromosuccinimide (14.24 g, 80.00 mMol, Aldrich) and the mixture was stirred at 25° C. for 0.5 h to give a light yellow solution. The reaction was carried out continually at 25° C. for 24 h to give a white precipitate, which was collected by filtration and then washed with distilled water (2*1 mL) followed by 95% ethanol (2*2 mL) to afford 2.216 g of pure 6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione (by NMR) as a white powder. The filtrate was poured into 200 ml ice water and the precipitate was collected by filtration, then washed with distilled water (2*2 mL) followed by 95% ethanol (2*2 mL) to afford 3.627 g of 6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione (with 1% impurity by NMR) which was dissolved into 1N NaOH (50 mL) and then acidified to pH=2 with 4N HCl to give a white cream precipitate. The precipitate was collected by filtration and washed with distilled water (2*2 mL) followed by 95% ethanol (2*2 mL) and dried in the air at 50° C. for 8 h, giving 3.517 g (total yield 89%) of pure 6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione (by NMR) as a white powder. Recrystallization from DMSO/H2 O) furnished white microcrystals. M.p. of 5,6-dibromo-1,4-dihydro-2,3-quinoxalinedione was measured: decomposed from 335° C. IR (KBr, cm-1): 3200, 1718, 1693. NMR (1 H, DMSO-d6): δ7.336 (s,2H); 11.962 (s,2H). HRMS: calcd. for C8 H4 Br2 N2 O2 (M+) m/z:317.8639 found: 317.8619. |
1% | With bromine In tetrachloromethane; ethanol; N,N-dimethyl-formamide | 32 Preparation of 6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione 6,7-Dibromo-1,4-dihydro-2,3-quinoxalinedione (Method C): To a stirred suspension of 1,4-dihydro-2,3-quinoxalinedione (550 mg, 3.39 mMol, Aldrich) in dry DMF (10 mL) was dropwise added a solution of bromine (1.07 g, 6.77 mMol, Aldrich) in dried DMF (0.5 mL) within 1 h and then the reaction was stirred at 25° C. for 30 h. Then, tetrachloromethane (10 mL) was added and the reaction mixture was stirred at 50° C. for 2 h. The reaction mixture was poured into ice water (50 mL) and the precipitate was collected by filtration and washed with distilled water (2*1 mL) followed by 95% ethanol (2*1 mL) to afford crude 6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione (with 1% impurity by NMR) as a white powder. The crude product was dissolved into 1N NaOH (10 mL) and then acidified to pH=2 with 4N HCl to give a white cream precipitate. The precipitate was collected by filtration and washed with distilled water (2*1 mL) followed by 95% ethanol (2*1 mL) and dried in the air at 50° C. for 8 h, to give 770 mg (yield 72%) of pure 6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione (by NMR) as a white powder. Recrystallization from DMSO/H2 O) furnished white microcrystals. M.p. of 6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione was measured: decomposed from 335° C. IR (KBr, cm-1): 3200, 1718, 1693. NMR (1 H, DMSO-d6): δ7.336 (s, 2H); 11.962 (s, 2H). HRMS: calcd for C8 H4 Br2 N2 O2 (M+) m/z: 317.8639 found: 317.8619. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chlorosulfonic acid | 21 Preparation of 6-Sulfonyl-1,4-dihydro-2,3-quinoxalinedione To 1,4-dihydro-2,3-quinoxalinedione (1.0 g, 6.2 mmol) was added all at once 3.0 mL of chlorosulfonic acid. The mixture was stirred under N2 at 60° C. for 2 h, allowed to come to room temperature and the solution added slowly dropwise to 25 mL of crushed ice. The resulting solid was vacuum filtered and rinsed with ice/H2 O. The white solid was further dried at 0.5 torr (25° C.) over CaSO4 to yield 1.1 g (68%). 1 H NMR (d6 -DMSO) δ7.07 (d, J7-8 =8.1, 1H, H8), 7.29 (dd, J7-8 =8.1, J6-7 =1.0, 1H, H7), 7.40 (d, J5-7 =1.0, 1H, H5). EIMS m/z 262 (M+2, 15), 260 (M+, 40), 225 (35), 105 (43), 36 (100, bp). EIHRMS calc. for C8 H5 ClN2 O4 S 259.9687, found 259.9645. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With conc. sulphuric acid; sulfuric acid | 4 1,2,3,4-Tetrahydro-2,3-dioxoquinoxaline-6-sulphonic acid EXAMPLE 4 1,2,3,4-Tetrahydro-2,3-dioxoquinoxaline-6-sulphonic acid 2,3(1H, 4H)-Quinoxalinedione (10 g) was added portionwise to a stirred mixture of 65% fuming sulphuric acid (10 ml) and conc. sulphuric acid (40 ml) at room temperature. After stirring for 30 minutes at 55°-60°, the mixture was worked up as in example 1 to give the hydrated crystalline product (15.3 g, mp. >300°). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With 18-crown-6 ether; tetrabutylammomium bromide; potassium carbonate In acetone Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With 18-crown-6 ether; tetrabutylammomium bromide; potassium carbonate In acetone Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With 18-crown-6 ether; tetrabutylammomium bromide; potassium carbonate In acetone Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With 18-crown-6 ether; tetrabutylammomium bromide; potassium carbonate In acetone Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With 18-crown-6 ether; tetrabutylammomium bromide; potassium carbonate In acetone Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With LiOH*H2O In N,N-dimethyl-formamide 3 equiv. of CuCl2 and 2 equiv. of N-compd., 4 equiv. of LiOH*H2O; layering of Et2O (1:1 v/v); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | Stage #1: quinoxaline-2,3-dione With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere; Stage #2: 1 ,6-dibromohexane In N,N-dimethyl-formamide at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With NaH; In water; N,N-dimethyl-formamide; | Example 6-3b 1,4-dimethylquinoxaline-2,3(1H,4H)-dione To a solution of NaH (2.5 g) in DMF (200 mL) was added quinoxaline-2,3(1H,4H)-dione (5 g) in portions, followed by the slow addition of methyl iodide (3.8 mL). The reaction mixture was stirred at ambient temperature for 4 hours, then water was added (200 mL) The resulting precipitate was collected by filtration and washed with water to afford 1,4-dimethylquinoxaline-2,3(1H,4H)-dione as a white solid in 95% yield. 1H NMR (400 MHz, DMSO-d6): delta, ppm: 3.50 (s, 6H), 7.25 (m, 2H), 7.38 (m, 4H). |
95% | With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 4h; | To a solution of NaH (2.5 g) in DMF (200 mL) was added quinoxaline-2,3(1H,4H)-dione (5 g) in portions, followed by the slow addition of methyl iodide (3.8 mL). The reaction mixture was stirred at ambient temperature for 4 hours, then water was added (200 mL) The resulting precipitate was collected by filtration and washed with water to afford 1,4-dimethylquinoxaline-2,3(1H,4H)-dione as a white solid in 95% yield. 1H NMR (400 MHz, DMSO-d6): delta, ppm: 3.50 (s, 6H), 7.25 (m, 2H), 7.38 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With LiOH*H2O In N,N-dimethyl-formamide High Pressure; DMF added to a mixt. of CuCl2, 1,4-dihydro-2,3-quinoxalinedione and LiOH; refluxed for 4 h; layered with Et2O; crystd. by slow mixing; filtered; washed once with DMF and twice with Et2O; dried in air; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In methanol at 20℃; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With pyridin-1-ium-1-yl[pyridin-1-ium-1-yl(sulfido)phosphinothioyl]sulfanyl-sulfido-thioxo-phosphane In dimethylsulfone at 165 - 175℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With acetic acid In ethanol; N,N-dimethyl-formamide Reflux; | 5.1.1. General procedure for synthesis of 3-(phenylimino/4-chlorophenylimino)-3,4-dihydroquinoxaline-2-(1H)-one 2a and 2b General procedure: To a constantly stirred solution of quinoxaline -2,3- dione (3.42 g, 0.02 mol) in 20 ml ethanol was added appropriate aromatic amines (aniline and p-chloro aniline 0.02 mol) in glacial acetic acid. To this mixture, 10 ml of DMF was added and then refluxed for 3-5 h. The reaction mixture was poured into crushed ice. The separated product was filtered, washed with distilled water and then dried in vacuum. Crude Schiff base was recrystallised from ethanol. |
85% | With acetic acid In ethanol Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.6% | With potassium carbonate In water at 20℃; for 7h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.3% | Stage #1: [2,2]bipyridinyl; molybdenum hexacarbonyl In tetrahydrofuran for 0.5h; Reflux; Inert atmosphere; Stage #2: quinoxaline-2,3-dione In tetrahydrofuran for 11h; Inert atmosphere; Reflux; | 2.2.1. Synthesis of [Mo2(bipy)(CO)4(DQ)2] complex (A) Mo(CO)6 (0.150 g, 0.568 mmol) and bipyridine (0.089 g,0.570 mmol) were mixed in 20 mL of THF, stirred and refluxed under nitrogen gas for 30 min. The obtained light red colored solution was allowed to cool down to room temperature, and a THF solution (10 mL) of DQ (0.092 g, 0.570 mmol) was then added drop wise. The reaction blend was then refluxed again at atmospheric pressure for 11 h, during which the reaction mixture turned into reddish brown color. The solid product was collected by filtration and washed withTHF, hot petroleum ether, and diethyl ether and then dried under vacuum. A slow diffusion of THF solvent into a concentrated DMF solution of the crude solid produced reddish brown microcrystals of the product which were then collected by filtration and dried under vacuum to give a pure reddish-brown product (0.17 g, 76.3%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.2% | Stage #1: [2,2]bipyridinyl; molybdenum hexacarbonyl In tetrahydrofuran for 0.5h; Reflux; Stage #2: quinoxaline-2,3-dione In tetrahydrofuran for 15h; Reflux; Schlenk technique; | 2.2.2. Synthesis [Mo2(bipy)(CO)2(DQ)3] complex (B) Mo(CO)6 (0.150 g, 0.568 mmol) and bipyridine (0.089 g,0.570 mmol), and 30 mL THF were stirred together and heated at reflux for 30 min, during which color of the reaction mixture turned into light red. The reaction blend was then allowed to get the room temperature (25 °C), and a THF solution (15 mL) of DQ (0.092 g, 0.570 mmol) was then added drop wise. The reaction mixture was heated to reflux temperature under reduced pressure in a Schlenk tube for 15 h, during which color of the reaction blend changed into a reddish orange. The solid material was isolated by filtration then washed several times with THF, hot petroleum ether, and then with diethyl ether. The crude product was crystallized by slow diffusion of THF solvent into DMF solution of the product to give reddish orange microcrystals of the complex. The microcrystals were collected by filtration and dried under vacuum to give 0.158 g of the desired product (62.2% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In methanol for 2h; Reflux; | Synthesis of ligand The synthesis of quinoxaline-2,3-(1,4H)-dione was done according to the literature [20]. To the hot methanolic solution of quinoxaline-2,3-(1,4H)-dione (0.005 mol) dry methanolic solution of 4-aminoantipyrine (0.005 mol) was added drop wise with constant stirring at room temperature. The mixture was refluxed for 2 h and the solid obtained was filtered, washed with ether and dried in vacou over anhydrous calcium chloride (Scheme 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With [bis(acetoxy)iodo]benzene; water In acetonitrile at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid In ethanol; N,N-dimethyl-formamide Reflux; | 5.1.1. General procedure for synthesis of 3-(phenylimino/4-chlorophenylimino)-3,4-dihydroquinoxaline-2-(1H)-one 2a and 2b General procedure: To a constantly stirred solution of quinoxaline -2,3- dione (3.42 g, 0.02 mol) in 20 ml ethanol was added appropriate aromatic amines (aniline and p-chloro aniline 0.02 mol) in glacial acetic acid. To this mixture, 10 ml of DMF was added and then refluxed for 3-5 h. The reaction mixture was poured into crushed ice. The separated product was filtered, washed with distilled water and then dried in vacuum. Crude Schiff base was recrystallised from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With Cs2CO3 In dimethyl sulfoxide at 20℃; for 3h; | 6a Example 6(a): Synthesis of 1-(3-methylbut-2-en-1-yl)-1,4-dihydroquinoxaline-2,3- dione (6b): To a solution of 1,4-dihydroquinoxaline-2,3-dione 6a (2 gm, 0.012 mol) in dry DMSO (40 mL) was added caesium carbonate (4.8 g, 0.014 mol), followed by 3,3-dimethylallyl bromide (1.42 mL, 0.012 mol) diluted in 5mL of DMSO and kept stirring for 3 hrs at room temperature reaction. The reaction mixture was added to cold water and extracted with ethyl acetate (3 X 100 mL). The combined organic layer was washed with brine anddried over Na2SO4, concentrated under reduced pressure, and subjected to flash chromatography over silica gel (40 % EtOAc: petroleum ether) to afford mono-alkylated compound 6b (1.1 gm, 38%) as brown solid.Data for 6b: ‘H NMR (500 MHz, DMSO-d6) ö = 12.04 (br. s., 1 H), 7.32 - 7.08 (m, 4 H),5.24 - 5.02 (m, 1 H), 4.85 - 4.61 (m, 2 H), 1.82 ‘(br. s., 3 H), 1.67 (br. s., 3 H); ‘3C NMR(126MHz, DMSO-d6) ö 154.9, 153.6, 136.1, 126.2, 125.8, 123.5, 123.2, 118.7, 115.7,115.0, 40.6, 25.3, 18.2. |
35% | With Cs2CO3 In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; | 4.2.1. 1-(3-Methylbut-2-en-1-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one(16) General procedure: To a solution of 1,3-dihydro-2H-benzo[d]imidazole-2-one 15(2 g, 0.014 mol) in dry DMF (40 mL) was added caesium carbonate(5.84 g, 0.017 mol), followed by 3,3-dimethylallyl bromide (1.89 mL,0.016 mmol) diluted in 5 mL of DMF and kept stirring for 2 h atroom temperature reaction. The reaction mixturewas added to coldwater and extracted with ethyl acetate (3 X100 mL). The combinedorganic layer was washed with brine and dried over Na2SO4,concentrated under reduced pressure, and subjected to flashchromatography over silica gel (20% EtOAc:PE) to afford monoalkylatedcompound 16 (1.6 g, 55%) as white solid. |
35% | With Cs2CO3 In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; | 4.2.1. 1-(3-Methylbut-2-en-1-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one(16) General procedure: To a solution of 1,3-dihydro-2H-benzo[d]imidazole-2-one 15(2 g, 0.014 mol) in dry DMF (40 mL) was added caesium carbonate(5.84 g, 0.017 mol), followed by 3,3-dimethylallyl bromide (1.89 mL,0.016 mmol) diluted in 5 mL of DMF and kept stirring for 2 h atroom temperature reaction. The reaction mixturewas added to coldwater and extracted with ethyl acetate (3 X100 mL). The combinedorganic layer was washed with brine and dried over Na2SO4,concentrated under reduced pressure, and subjected to flashchromatography over silica gel (20% EtOAc:PE) to afford monoalkylatedcompound 16 (1.6 g, 55%) as white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In methanol; water for 6h; Reflux; | 2.3. Synthesis of ligand The synthesis of quinoxaline-2,3-(1,4H)-dione was done according to the literature [7]. The ligand, N2,N3-bis(4-nitrophenyl)-quinoxaline-2,3-diamine (L) was synthesized by the reaction between quinoxaline-2,3-(1,4H)-dione and 4-nitroaniline. To the hot methanolic solution of quinoxaline-2,3-(1,4H)-dione (0.002mol)dry methanolic solution of 4-nitroaniline (0.004mol) was added dropwise with constant stirring at room temperature. To the above solution, few drops of concentrated hydrochloric acid was added. The mixture was refluxed for ca. 6 h and the resultant solid formed was cooled to roomtemperature, filtered, washed with ether and dried in vacou over anhydrous calcium chloride. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In methanol for 2h; Reflux; | Synthesis of Ligand The synthesis of quinoxaline-2.3-(1,4H)-dione was prepared according to the method given by Philips [11]. The ligand, 1 was synthesized by the following method. To the hot methanolic solution of quinoxaline-2.3-(1,4H)-dione (0.002 mol), methanolic solution of 3-nitroaniline (0.004 mol) was added drop wise with constant stirring at room temperature (Fig. 1). The mixture was refluxed for 2 h and the resultant solution was cooled to room temperature, the solid product formed was filtered, washed with ether and dried in vacuum over anhydrous calcium chloride. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
420 mg | With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 6h; Sealed tube; | 1 Step 1. A mixture of quinoxaline-2,3(lH,4H)-dione (200 mg, 1.23 mmol), cesium carbonate (884 mg, 2.71 mmol) and benzyl 2-bromoacetate (0.41 mL, 2.6 mmol) in DMF (8 mL) was sealed and heated in an oil bath at 80 °C for 6 h. The reaction mixture was poured it into water (50 mL) and extracted with EtOAc. The organic component was washed with 5% citric acid and brine, dried over MgSCn, filtered and dried in vacuo. The residue was triturated with 4: 1 hexanes-EtOAc to afford dibenzyl 2,2'-(2,3-dioxo-2,3- dihydroquinoxaline-l,4-diyl)diacetate (420 mg) as a light yellow solid. LC-MS retention time = 1.23 min; m/z = 459.2 [M+H]+. (Column: Waters Aquity BEH C18 2.1 X 50 mm 1.7^m-particles; Solvent A = 100% Water/ 0.05% TFA; Solvent B = 100% Acetonitrile/0.05% TFA; Flow Rate = 0.8 mL/min. Start % B = 2; Final % B = 98; Gradient Time = 1.5 minutes; Wavelength = 220 nm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With hydrazine hydrate for 4h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: hydrazine hydrate monohydrate / 4 h / Reflux 2: 3 h / Reflux 3: trichlorophosphate / toluene; N,N-dimethyl-formamide / 3 h / Reflux | ||
Multi-step reaction with 3 steps 1: thionyl chloride / dichloromethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 20 °C 3: 4 h / Reflux | ||
Multi-step reaction with 3 steps 1: thionyl chloride / 1,2-dichloro-ethane 2: hydrazine hydrate monohydrate / ethanol / 20 °C 3: Heating |
Multi-step reaction with 3 steps 1: thionyl chloride / N,N-dimethyl-formamide; 1,2-dichloro-ethane / 2 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 4 h / 20 °C 3: 1 h / Reflux | ||
Multi-step reaction with 3 steps 1: thionyl chloride; N,N-dimethyl-formamide / 1,2-dichloro-ethane / 2 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 16 h 3: 1 h / Reflux | ||
Multi-step reaction with 3 steps 1: thionyl chloride / dichloromethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 20 °C 3: 4 h / Reflux | ||
Multi-step reaction with 3 steps 1: thionyl chloride / 1,2-dichloro-ethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 20 °C 3: ethanol / 4 h / Reflux | ||
Multi-step reaction with 3 steps 1: thionyl chloride / 1,2-dichloro-ethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / 20 °C 3: 4 h / Reflux | ||
Multi-step reaction with 3 steps 1: thionyl chloride / N,N-dimethyl-formamide; 1,2-dichloro-ethane / 2 h / Heating 2: hydrazine monohydrate; triethylamine / ethanol / 4 h / 20 °C 3: 1 h / Heating | ||
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide; thionyl chloride / 1,2-dichloro-ethane / 2 h / Reflux 2: hydrazine / ethanol / 4 h 3: 1 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With hydrogenchloride In water at 100℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With copper(l) iodide; potassium carbonate; 1-(2-pyridyl)-3-(2-pyridyl)-1,3-propanedione In N,N-dimethyl-formamide at 150℃; for 30h; | E 1,4-bis[1,1';3',1"]terphenyl-5'-yl-1,4-dihydroquinoxaline-2,3-dione 5.6 g (40 mmol) of 6-phenyl-1H-quinazoline-2,4-dione and 30 g (85 mmol) of 4-iodobenzene and 44.7 g (320 mmol) of potassium carbonate, 3 g (16 mmol) of copper(I) iodide and 3.6 g (16 mmol) of 1,3-di(pyridin-2-yl)propane-1,3-dione are stirred in 100 mL of DMF at 150° C. for 30 h. The solution is diluted with water and extracted twice with ethyl acetate, and the combined organic phases are dried over Na2SO4 and concentrated by rotary evaporation. The residue is recrystallized from toluene and finally sublimed under high vacuum (p=5*10-5 mbar). The purity is 99.9%. The yield is 14 g (23 mmol), 61% of theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In N,N-dimethyl-formamide at 150℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.6% | With hydrogenchloride In ethanol; water | General procedure General procedure: An equimolar mixture of compound 1/2 (0.015 mol), andcompound a-g (quinoxalin- 2, 3 (1H, 4H) dione (a), 2, 3-biphenyl qunoxalin-7-sulfonamide (b), 2,3 -biphenyl quinoxaline(c), 2,3-biphenyl qunoxalin-7-sulphonyl chloride(d), benzoin (e), salicylic acid (f), and isatin (g) were placedin a 250-mL beaker containing 100 mL of 35% HCl and35 mL of 10% formaldehyde. The reaction mixture washeated at 70-85 °C and stirred for 5-8 h using magneticstirrer (depending on the derivative). The progress of productformation was monitored by periodical examination byTLC technique. At the end of the reaction, the resultedsolution was neutralized using 20% v/v ammonia (the Blancreaction; Leonid et al. 1977) and then it was refrigerated forovernight. The formed crystals were filtered, washed withpurified water and subjected to further purification processusing double recrystallization and preparative TLC. All ofthe synthesized compounds were tested for their homogeneityusing HPLC analyses. Subsequently, these compoundswere characterized using physical and spectral dataand their corresponding physical and spectral data areshown in Tables 1, 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65.5% | With hydrogenchloride In ethanol; water | General procedure General procedure: An equimolar mixture of compound 1/2 (0.015 mol), andcompound a-g (quinoxalin- 2, 3 (1H, 4H) dione (a), 2, 3-biphenyl qunoxalin-7-sulfonamide (b), 2,3 -biphenyl quinoxaline(c), 2,3-biphenyl qunoxalin-7-sulphonyl chloride(d), benzoin (e), salicylic acid (f), and isatin (g) were placedin a 250-mL beaker containing 100 mL of 35% HCl and35 mL of 10% formaldehyde. The reaction mixture washeated at 70-85 °C and stirred for 5-8 h using magneticstirrer (depending on the derivative). The progress of productformation was monitored by periodical examination byTLC technique. At the end of the reaction, the resultedsolution was neutralized using 20% v/v ammonia (the Blancreaction; Leonid et al. 1977) and then it was refrigerated forovernight. The formed crystals were filtered, washed withpurified water and subjected to further purification processusing double recrystallization and preparative TLC. All ofthe synthesized compounds were tested for their homogeneityusing HPLC analyses. Subsequently, these compoundswere characterized using physical and spectral dataand their corresponding physical and spectral data areshown in Tables 1, 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
148 mg (30%) | In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; | D. 2,3-Diamino-5-fluorobenzotrifluoride To a stirred mixture of <strong>[344-29-6]2-amino-5-fluoro-3-nitrobenzotrifluoride</strong> (554 mg, 2.47 mmol) in ethanol (10 mL) was added SnCl2 ·2H2 O (2.78 g, 12.36 mmol) in one portion. The mixture was refluxed at 80 C. (oil bath 90 C.) for 1 h, cooled to room temperature and ice water (20 g) was added. It was adjusted to pH=7 and extracted with ethyl acetate. The extract was dried over Mg2 SO4 and evaporated to give 148 mg (30%) of 2,3-diamino-5-fluorobenzotrifluoride as a brown solid. 1 H NMR (CDCl3): delta3.666 (s, 2H); 3.676 (s, 2H); 6.610 (dd, 1H, J1 =2.4 Hz, J2 =9.0 Hz), 6.703 (dd, 1H, J1 =2.4 Hz, J2 =9.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | 1-Dodecyl-1,4-dihydro-<strong>[15804-19-0]quinoxaline-2,3-dione</strong>, 2: a solution ofpreviously prepared 1,4-dihydro<strong>[15804-19-0]quinoxaline-2,3-dione</strong> [21] (1.5g,9.25 mmol), and potassium carbonate (0.42 g, 3.04 mmol) indimethylformamide (5 ml) was kept under magnetic stirring for1 h at 60 C, and then cooled to 40 C. Next, dodecylbromide(0.768 g, 3.08 mmol)was added dropwise (during 2 h), and the finalsolutionwas maintained under magnetic stirring for 24 h. After thistime, reactional medium was diluted with water (25 ml) andextraction using ethyl acetate (3 30 ml) was performed. Theresulting organic layer was dried with magnesium sulfate, thesolvent eliminated under vacuum, and the solid residue purified bycolumn chromatography (silica gel as stationary phase and hexaneethylacetate 20:1 v/v as eluent) to afford a pure product as a lightgrey solid after being kept in a desiccator under vacuum in thepresence of calcium chloride for five days. Yield: 56%. Mp: 49 C. IR ymax (cm1): 3334 (NeH), 3083 (NeH), 2952 (CeH), 2917(CeH),1665 (C]O), 1605 (NeH), 1464 (CeH), 1298 (CeN), 759(AreH). 1H NMR (300 MHz, CDCl3) d (ppm): 8.15, (d, J 8 Hz, 1H,ArH), 7.66 (m, 1H, ArH), 7.22 (m, 1H, ArH), 6.74, (d, J 8 Hz, 1H,ArH), 4.29 (br, 1H, NH), 3.80 (t, J 7 Hz, 2H, NCH2), 1.74 (m, 2H,CH2), 1.27 (m, 18H, CH2), 0.88 (t, J 6 Hz, 3H, CH3). Elementalanalysis: Calcd: C, 72.69; H, 9.15; N, 8.48; Found: C, 72.71; H, 9.21;N, 8.50. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h; | 4.1 5.1.4.1 Preparation of ethyl 2-(2,3-dioxo-3,4-dihydroquinoxalin-1(2H)-yl)acetate (25) 60% NaH in oil (88 mg, 2.2 mmol) was added to a solution of quinoxaline-2,3-dione (324 mg, 2.0 mmol) in DMF (20 mL) with cooling in an ice bath. Then, ethyl bromoacetate (0.21 mL, 1.9 mmol) was also added to the mixture and the resulting mixture was stirred at room temperature for 2 h. The reaction was quenched with water and extracted with AcOEt. The organic layer was washed with brine and dried over Na2SO4. Filtration and evaporation in vacuo gave a crude solid. The crude solid was suspended in CHCl3 (5 mL) and the insoluble material was collected by filtration to give 25 (117 mg, 25%): 1H NMR (DMSO-d6, 300 MHz, δ; ppm), 12.20 (1H, brs), 7.31-7.28 (1H, m), 7.23-7.14 (3H, m), 4.97 (2H, s), 4.16 (2H, q, J = 7.2 Hz), 1.21 (3H, t, J = 7.2 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: thionyl chloride / 1,2-dichloro-ethane 2: hydrazine hydrate / ethanol / 20 °C 3: Heating 4: thiourea / ethanol | ||
Multi-step reaction with 4 steps 1: thionyl chloride / dichloromethane / 4 h / Reflux 2: hydrazine hydrate / ethanol / 20 °C 3: 4 h / Reflux 4: potassium hydroxide; carbon disulfide / ethanol / 6 h / Reflux | ||
Multi-step reaction with 4 steps 1: thionyl chloride / 1,2-dichloro-ethane / 4 h / Reflux 2: hydrazine hydrate / 20 °C 3: 4 h / Reflux 4: thiourea; potassium hydroxide / ethanol; water / 6 h / Reflux |
Multi-step reaction with 4 steps 1: thionyl chloride / N,N-dimethyl-formamide; 1,2-dichloro-ethane / 2 h / Heating 2: hydrazine hydrate; triethylamine / ethanol / 4 h / 20 °C 3: 1 h / Heating 4: potassium hydroxide; thiourea / ethanol / 6 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With hydrogenchloride; In water; at 80℃; for 2h; | A mixture of o-phenylenediamine (10.40 g, 100 mmol), hydrochloric acid (4 mol/L, 58 mL, 24 mmol) and dimethyl oxalate (14 mL, 100 mmol) was stirred at 80 C for 2 h. After completion confirmed by TLC, the reaction was cooled to room temperature. The resulting solid was filtered, washed with water (250 mL), and subsequently dried under vacuum to afford 2a as white solid (14.11 g, 90 %). M. P.: > 300 C. 1H NMR (400 M, DMSO-d6) delta 11.91 (s, 2H), 7.13 - 7.06 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With hydroxylamine hydrochloride; water; Thiamine hydrochloride; In 1,4-dioxane; at 90℃; for 0.833333h; | General procedure: A mixture of ketone 1 (2 mM), hydroxylamine hydrochloride (3 mM) and thiamine hydrochloride (0.4 mM) was taken in 10mL dioxane:H2O (9:1) in a round-bottom flask and heated at 90 C for specific time (30-90 min). The progress of the reaction was monitored using thin layer chromatography (tlc). After completion of the reaction, the reaction flask was cooled to room temperature. The residue was taken in ethyl acetate (30 ml), washed with water (2x15 ml), brine (1x15 ml) and the organic layer was dried (anhyd. Na2SO4). The resulting ethyl acetate solution was concentrated and the desired amides 2 (75-95% yield) are obtained by recrystallization from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: thionyl chloride / dichloromethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 20 °C 3: 4 h / Reflux 4: potassium hydroxide / ethanol; water monomer / 10 h / Reflux | ||
Multi-step reaction with 4 steps 1: thionyl chloride / 1,2-dichloro-ethane / 4 h / Reflux 2: hydrazine hydrate monohydrate / 20 °C 3: 4 h / Reflux 4: potassium hydroxide / ethanol; water monomer / 10 h / Reflux | ||
Multi-step reaction with 4 steps 1: thionyl chloride / N,N-dimethyl-formamide; 1,2-dichloro-ethane / 2 h / Heating 2: hydrazine monohydrate; triethylamine / ethanol / 4 h / 20 °C 3: 1 h / Heating 4: potassium hydroxide / ethanol / 0.17 h / Heating |
Multi-step reaction with 3 steps 1.1: thionyl chloride / 1,2-dichloro-ethane / 5 h 2.1: hydrazine monohydrate; triethylamine / ethanol / 4 h / 20 °C 3.1: 2 h 3.2: 3 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With acetic acid Heating; | 16 Synthesis of compound A27: The compound A26 (1.63g, 10mmol), urea (0.6g, 10mmol) and 10ml of acetic acid were heated overnight, the reaction mixture was cooled to room temperature, the resulting solid was filtered, and washed with ethanol and water to obtain A27 (1.21g, 65%) ) |
[ 1910-90-3 ]
6-Bromoquinoxaline-2,3(1H,4H)-dione
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[ 2050-85-3 ]
N,N'-(1,2-Phenylene)diacetamide
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[ 262368-30-9 ]
N-(4-Aminophenyl)-N-methyl-2-(4-methylpiperazin-1-yl)acetamide
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[ 25983-13-5 ]
6,7-Dichloroquinoxaline-2,3(1H,4H)-dione
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[ 1910-90-3 ]
6-Bromoquinoxaline-2,3(1H,4H)-dione
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[ 25983-13-5 ]
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[ 106595-91-9 ]
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Similarity: 0.76
[ 80636-30-2 ]
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Similarity: 0.76
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P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
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 |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
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 |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
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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