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CAS No. : | 1226-42-2 | MDL No. : | MFCD00008405 |
Formula : | C16H14O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YNANGXWUZWWFKX-UHFFFAOYSA-N |
M.W : | 270.28 | Pubchem ID : | 71043 |
Synonyms : |
p-Anisil
|
Num. heavy atoms : | 20 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.12 |
Num. rotatable bonds : | 5 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 74.53 |
TPSA : | 52.6 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | Yes |
Log Kp (skin permeation) : | -5.59 cm/s |
Log Po/w (iLOGP) : | 2.7 |
Log Po/w (XLOGP3) : | 3.32 |
Log Po/w (WLOGP) : | 2.77 |
Log Po/w (MLOGP) : | 1.57 |
Log Po/w (SILICOS-IT) : | 3.35 |
Consensus Log Po/w : | 2.74 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.72 |
Solubility : | 0.0513 mg/ml ; 0.00019 mol/l |
Class : | Soluble |
Log S (Ali) : | -4.1 |
Solubility : | 0.0214 mg/ml ; 0.0000793 mol/l |
Class : | Moderately soluble |
Log S (SILICOS-IT) : | -5.07 |
Solubility : | 0.00231 mg/ml ; 0.00000855 mol/l |
Class : | Moderately soluble |
PAINS : | 1.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 1.68 |
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 |
---|---|---|
100% | Reflux | Step 1. Preparation of l 2-bis(4-hydroxyphenyl)ethane-l,2-dione 4,4'-dimethoxybenzil (2.0 g, 7.41 mmol) was dissolved in 30 mL of hydrogen bromide and 10 mL of acetic acid glacial. The reaction was stirred at reflux temperature overnight. The mixture was extracted with ethyl acetate and the organic phase was washed with water, dried over sodium sulphate. Concentration under vaccum gave the title compound as a yellow solid (1.9 g, quantitative). |
94% | With hydrogen bromide; acetic acid In water for 24 h; Reflux | Into a 100 mL round-bottomed two-necked flask equipped witha magnetic stirrer bar and a reflux condenser, 4,4'-dimethoxybenzil(2 g, 0.0075 mmol), aqueous HBr (15 mL, 48percent) and glacialacetic acid (15 mL) were placed. The reaction mixture was refluxedfor 24 h, after cooling to room temperature, was poured into100 mL water. Ethyl acetate was added to the mixture to give twophases of which the organic phase containing the product wasseparated and dried over magnesium sulfate for 12 h. The solventwas removed under reduced pressure and the obtained yellowprecipitate was washed thoroughly with water and then dried in avacuum oven at 80 8C. Yield: 94percent (1.7 g) and m.p.: 229–231 8C. FTIR(KBr) at cm 1: 3400 (OH phenol), 3045 (C–H aromatic), 1646(C55O), 1576 (C55C), 1223 (C–O). 1H NMR (400 MHz, DMSO-d6,): d6.91–6.95 (d, 4H, J = 8.0 Hz), 7.73–7.77 (d, 4H, J = 8.0 Hz), 10.84 (s,2H). |
94% | With hydrogen bromide In water; acetic acid for 24 h; Reflux | Into a 100 mL round-bottomed two-necked flask equipped with a magnetic stir bar and a reflux condenser, 4,4'-dimethoxy benzil (2 g, 0.0075 mol), aqueous HBr (15 mL, 48percent) and glacial acetic acid (15 mL) were placed. The reaction mixture was refluxed for 24 h, and then poured in 100 mL water after cooling to room temperature. Ethyl acetate was added to the mixture to give two phases of which the organic phase containing the product was separated and dried over magnesium sulfate for 12 h. The solvent was removed under reduced pressure and the obtained yellow precipitate was washed thoroughly with water and then dried in a vacuum oven at 80 °C. Yield: 94percent (1.7 g), and melting point: 229-231 °C. FT-IR (KBr) at cm-1: 3400 (OH phenol), 3045 (C-H aromatic), 1646 (C=O), 1576 (C=C), 1223 (C-O). 1H NMR (400 MHz, DMSO-d6,): δ 6.91-6.95 (d, 4H, J = 8.0 Hz), 7.73-7.77 (d, 4H, J = 8.0 Hz), 10.84 (s, 2H). |
90% | for 24 h; Reflux; Inert atmosphere | A mixture of 4,4'-dimethoxybenzil (2.50 g, 0.0092 mol), glacial acetic acid (25 mL), and HBr (30 mL) was refluxed for 12 h under N2. After cooling, 5 mL HBr was added and mixture was refluxed for another 12 h. Upon completion of the reaction (as witnessed by TLC), the medium was poured into 200 mL deionized water. The organic product was extracted with 220 mL ethyl acetate. The organic phase was thoroughly washed with water in order to remove all acids and then dried over magnesium sulfate. The product was obtained as crystal after evaporation of the solvent in a rotary evaporator. The yield after drying in a vacuum oven at 80 °C was 90percent (1.79 g) with melting point of 120 °C. FT-IR (KBr, cm 1): 3031 (OH stretching), 1633 (C55O stretching), 1612 (C55C stretching), 1226 (C–O–C stretching). 1H NMR (400 MHz, DMSO-d6): d = 10.84 (2H OH, s), 6.91–7.77 (8H, m) ppm. C14H10O4: calculated C, 69.42percent; H, 4.13percent; N, 0percent; found C, 69.38percent; H, 4.16percent; N, 0percent. m/e: 242.06, 243.06, 244.06. |
89% | at 180℃; for 48 h; | A mixture of 1,2-bis(4-methoxyphenyl)-ethane-1,2-dione prepared according to example 1 (7.275 g, 26.91 mmol) and pyridine hydrochlorate (15.55 g, 134.5 mmol) under an atmosphere of nitrogen is heated to 180° C. for 2 days. After returning to ambient temperature, the mixture is diluted with ethyl acetate and water. The aqueous phase is extracted with ethyl acetate and the recombined organic phases are dried on magnesium sulfate, filtered and concentrated under reduced pressure. The residue is purified by flash chromatography on a silica gel (petroleum ether/ethyl acetate 10/1 to 2/1) to yield 5.789 g (89percent) of a white solid. δH (300 MHz, MeOH-d) 6.91 (d; J 9.0; 4H), 7.82 (d; J 9.0; 4H). |
75% | With hydrogen bromide; acetic acid In water for 12 h; Reflux | The synthesis of 2 needs two steps. Firstly, a mixture of 1,2-bis(4-methoxyphenyl) ethane-1,2-dione (3 g, 11 m mol), glacial acetic acid (30 ml) and HBr (48percent, 100 ml) were added into a three-neck round bottom flask orderly, heated to reflux and stirred for 12 h. Then the mixture was cooled to room temperature and brown precipitation was observed. Then the precipitate was separated by filtration and washed with distilled water three times to give 1,2-bis(4-hydroxyphenyl) ethane-1,2-dione, yield: 75percent. Secondly, 1,2-bis(4-hydroxyphenyl) ethane-1,2-dione (2.0 g, 8.2 m mol), 1 - bromine decane (4.04g, 3.78 ml),anhydrous potassium carbonate (2.4g, 0.24 mol) and Tetra-nbutylammoniumbromide (1.33 g, 4.13 m mol) were dissolved in DMF (120 ml). The solution was heated to 120 deg.C and reacted for 90 min. After reaction, the solution was cooled to room temperature, added with water, oscillated by ultrasonic instrument.The cream-color deposit was filtered and washed by distilled water several times to give the target product (2) with a high productivity (about 90percent). |
4 g | With hydrogen bromide; acetic acid In water at 70 - 110℃; for 70 h; | Synthesis Example 1 Synthesis of 4,4′-dihydroxybenzil (0057) 4,4′-Dimethoxybenzil (5.0 g) was dissolved in acetic acid (95 mL). To the solution, 48 mass percent aqueous HBr (31.2 g) was added dropwise at 70° C. over 10 minutes. After addition of HBr, the mixture was stirred at 110° C. for 70 hours. Subsequently, water (150 g) was added to the mixture, to thereby crystallize the product. The crude crystals were recovered through filtration and washed with water (250 g), followed by drying, to thereby yield 4.0 g of 4,4′-dihydroxybenzil as a target product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | at 100℃; for 5 h; | Example 1: Synthesis of 4-2-[3.5-bis(trifluoromethyl')phenyl]-4.5-bis[4-methoχphenyl*)imidazol- 1 -yl-methyl-benzamide f Apoptozole 1); <n="13"/>[64][65] To a stirred solution of ammonium acetate (0.6 g, 8.0 mmol) in acetic acid (5 mL) was added 3,5-bis(trifluoromethyl)benzaldehyde (0.3 μL, 1.7 mmol), 4.4'-dimethoxybenzil (0.5 g, 1.7 mmol) and 4-(aminomethyl)benzamide (0.2 g, 1.3 mmol) at 100 °C. After stirring for 5 h, the reaction mixture was diluted with CH Cl and washed with H 2 O and brine. The organic layer was dried over anhydrous MgSO 4 , filtered and concentrated under the reduced pressure. The crude product was purified by flash column chromatography (3:1 to 1:1 hexane/EtOAc) to give a pure product (0.4 mmol, 30 percent): 1K NMR (250 MHz, CD3OD) δ 8.82 (s,2 H), 8.67 (s, 2 H), 8.40 (d, 2 H, J = 10.0), 8.06 (d, 2 H, J = 8.8), 7.90 (d, 2 H, J = 8.1), 7.62-7.58 (m, 4 H), 7.45 (d, 2 H, J = 8.8), 5.91 (s, 2 H), 4.45 (s, 3 H), 4.40 (s, 3 H) 13C NMR (125 MHz, CD3OD) δ 171.6, 162.0, 160.5, 145.9, 142.4, 140.1, 134.5, 134.3, 133.7, 133.4, 133.2, 132.5, 130.4, 129.6, 129.4, 127.6, 127.2, 123.7, 123.1, 115.8, 114.8, 55.9, 55.8, 40.5 MALDI- TOF-MS calcd for C H F N O (M+Na)+ 648.18, found 648.18. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With air; magnetic magnetite nanoparticles; In ethanol; at 80℃; for 9.0h;Sealed tube; Green chemistry; | General procedure: A mixture of alpha-hydroxy ketone (0.2 mmol), Fe3O4·MNPs (30 mol%)and ethanol (1.5 mL) were placed in a sealed tube. The reaction mixturewas heated at 80 C. After completion of reactions, monitored by thinlayer chromatography, the catalyst was separated magnetically. Thereaction solution was concentrated under reduced pressure and thecrude material was purified by preparative thin-layer chromatographywith petroleum ether-EtOAc as eluent. |
92% | With tert.-butylhydroperoxide; In dodecane; acetonitrile; at 65℃; for 1.0h; | General procedure: A 25 mL round bottom flask was charged with alcohol (1.0 mmol), catalyst (0.02 equiv.), MeCN (5 mL), TBHP (1.5 M solution in dodecane; 1.5 equiv.) and then stirred at 65 C for 1 h. According to Table 2, all reactions require 1 h. At the end of the reaction, the catalyst was filtered at room temperature over membrane filter paper and reused for subsequent runs. The filtrate so obtained was concentrated under reduced pressure and the residue was dissolved in dichloromethane (20 mL). The organic layer was washed with brine solution (10 mL 3×). The organic layer was dried over anhydrous MgSO4 and then, concentrated under reduced pressure. Product was purified by column chromatography over silica gel. The isolated yield of the obtained product was found to be 94% and the conversion was determined by the GC-MS analysis. The purity of the products was determined by comparing the 1H NMR spectra of the products with those of authentic samples. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetic acid at 20℃; Heating / reflux; | a Preparation of 2-n-pentyl-5,6-bis-(4-methoxyphenyl)-1,2,4-triazin-3-one (Compound 8); a) 5,6-bis-(4-methoxyphenvl)-1,2,4-triazin-3-thione A mixture of 4,4'-dimethoxybenzil (13.6 g, 50 mmol) and 6.06 g of thiosemicarbazide (66.5 mmol) in 50 ML of glacial acetic acid were stirred at room temperature then refluxed overnight.The cooled reaction mixture was diluted with 150 ML of water and filtered.The solids were washed with water and dried.The crude product was heated with 55 ML of ethyl acetate, cooled, filtered and dried to give 10.1 g of 5,6-bis-(4-methoxyphenyl)-1,2,4-triazin-3-thione, mp 228-232° C. |
|
In acetic acid Heating / reflux; | ||
With hydrogenchloride In ethanol; water at 120℃; for 0.333333h; Microwave irradiation; | General procedure for the synthesis of compounds 2a-f General procedure: To a stirred solution of appropriate 1,2-diketone 1a-f(1 mmol) and thiosemicarbazide (1.1 mmol) in a mixture ofwater and ethanol (1:1), was added a few drops of concentratedhydrochloric acid and resulting mixture was irradiatedunder microwave at 130 °C for 20 min. After coolingto room temperature, it was filtered and washed with waterto give the desired product. This procedure in detail alongwith structural characterization data of compounds has beenreported in our recently published study (Irannejad et al.2014, 2015). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With aluminum (III) chloride at 0 - 20℃; for 4h; | 1 Synthesis of 1,2-bis(4-methoxyphenyl)-ethane-1,2-dione(1) Oxalyl chloride (4.71 ml, 55.2 mmol) at 0° C. is slowly added to a mixture of anisole (10.8 g, 100 mmol) and aluminum chloride (33.33 g, 250 mmol). The mixture is stirred at ambient temperature for 4 hours. After cooling, it is poured into iced water and extracted with dichloromethane. The organic phases collected are washed with 2 N HCl then with brine and are dried on magnesium sulfate. After filtration and concentration under reduced pressure, the residue is recrystallized in ethanol. The resulting precipitate is filtered, washed several times in ethanol and dried to yield 9.80 g (66%) of pure product in the form of a yellow solid. δH (200 MHz, CDCl3) 3.93 (s; 6H), 6.99 (d; J 7.8; 4H), 7.99 (d; J 7.8; 4H). |
66% | With aluminum (III) chloride at 0 - 20℃; for 4h; | 1 Synthesis of 1,2-bis(4-methoxyphenyl)-ethane-1,2-dione(1) Oxalyl chloride (4.71 ml, 55.2 mmol) at 0° C. is slowly added to a mixture of anisole (10.8 g, 100 mmol) and aluminum chloride (33.33 g, 250 mmol). The mixture is stirred at ambient temperature for 4 hours. After cooling, it is poured into iced water and extracted with dichloromethane. The organic phases collected are washed with 2 N HCl then with brine and are dried on magnesium sulfate. After filtration and concentration under reduced pressure, the residue is recrystallized in ethanol. The resulting precipitate is filtered, washed several times in ethanol and dried to yield 9.80 g (66%) of pure product in the form of a yellow solid. δH (200 MHz, CDCl3) 3.93 (s; 6H), 6.99 (d; J 7.8; 4H), 7.99 (d; J 7.8; 4H). |
44% | With titanium tetrachloride In dichloromethane at -20 - 0℃; for 1h; | 4-Methoxybenzene (8.3 g, 0.077 mol)Is dissolved in dichloromethane (100 ml), the temperature is lowered to -20 ° C, and titanium chloride (8.47 ml, 0.077 mol) is slowly added dropwise while maintaining the temperature.While maintaining the temperature of the solution, oxalyl chloride (3.44 ml, 0.039 ml) was slowly added dropwise and stirred for 1 hour while raising the temperature to 0 ° C.After completion of the reaction, the reaction mixture is washed with 3N hydrochloric acid solution (100 ml), water (100 ml) and saturated brine (50 ml), then excess water is removed with anhydrous magnesium sulfate and distilled under reduced pressure. The concentrated solid was recrystallized from isopropyl alcohol to obtain 4.6 g (yield: 44%) of the objective 44,4'-dimethoxybenzyl as a yellow solid. |
With carbon disulfide; aluminium trichloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With sodium hydroxide In ethanol for 6h; Reflux; Inert atmosphere; Schlenk technique; | 2.2 4.2.2. 3,4-(p-MeOPh)2-2,5-Ph2(C4CO) (5) 4,4'-Dimethoxybenzil (2.90 g, 10.36 mmol) and 1,3-diphenylacetone (2.26 g, 10.36 mmol) were dissolved in 30 mL ethanol in a 100 mL two-neck round bottom flask equipped with a condenser. The reaction mixture was warmed up nearly to the boiling point of ethanol, followed by the slow addition of a solution of 0.36 g NaOH in 3 mL ethanol. When the addition was finished, the reaction mixture was refluxed for 6 h followed by cooling to 0 °C. The crude product was then filtered and washed several times with deionized water and ethanol, and dried under vacuum overnight at room temperature to afford 5 (4.15 g, 90%) as a dark purple solid. IR (KBr) in cm-1: 1707 (s, νC=O). 1H NMR (400 MHz, CD2Cl2): δ 3.77 (s, 6H, OCH3), 6.72 (d, 4H, J = 8.0 Hz, aromatic H), 6.86 (d, 4H, J = 8.0 Hz, aromatic H), 7.20-7.29 (m, 10H, aromatic H). 13C{1H} NMR (100 MHz, CD2Cl2): δ 55.6 (OCH3), 113.7-160.3 (8 resonances, aromatic), 125.2 (C2,5 of cyclopentadienone or Cp-dienone), 154.7 (C3,4 of Cp-dienone), 200.6 (C1 of Cp-dienone). MS (ESI) m/z (relative intensity) [M+H]+: 445. |
87% | With sodium hydroxide In methanol for 1.25h; Reflux; | |
86% | With potassium hydroxide In ethanol at 80℃; |
81% | With potassium hydroxide In ethanol for 3h; Reflux; | |
77% | With potassium hydroxide In ethanol for 1.5h; Reflux; | |
75% | With sodium hydroxide In ethanol at 70℃; for 0.416667h; Microwave irradiation; | |
66% | Alkaline conditions; | |
64.3% | With potassium hydroxide In ethanol at 75℃; for 0.5h; | |
With potassium hydroxide; ethanol | ||
With potassium hydroxide In methanol | ||
With potassium hydroxide In ethanol at 80℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With ammonium chloride; zinc In tetrahydrofuran at 20℃; for 1h; | |
92% | With water; zinc trifluoromethanesulfonate; zinc In 1,4-dioxane at 90℃; for 4h; Inert atmosphere; Schlenk technique; Green chemistry; | |
88% | With titanium(IV) iodide In acetonitrile at 0 - 20℃; for 5.3h; |
81% | With sodium hydrogen selenide; acetic acid In tetrahydrofuran; ethanol for 1.5h; Ambient temperature; | |
56% | With acetic acid; zinc at 20℃; Inert atmosphere; | |
With sodium hydroxide; aluminum nickel; toluene | ||
With zinc In water; N,N-dimethyl-formamide | ||
With 3,5,5-trimethyl-2-morpholinon-3-yl In chloroform-d1 at 50℃; | ||
With sodium dithionite; sodium carbonate In diethyl ether; water at 20℃; for 120h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydrogen bromide; acetic acid;Reflux; | Step 1. Preparation of l 2-bis(4-hydroxyphenyl)ethane-l,2-dione 4,4'-dimethoxybenzil (2.0 g, 7.41 mmol) was dissolved in 30 mL of hydrogen bromide and 10 mL of acetic acid glacial. The reaction was stirred at reflux temperature overnight. The mixture was extracted with ethyl acetate and the organic phase was washed with water, dried over sodium sulphate. Concentration under vaccum gave the title compound as a yellow solid (1.9 g, quantitative). |
94% | With hydrogen bromide; acetic acid; In water; for 24h;Reflux; | Into a 100 mL round-bottomed two-necked flask equipped witha magnetic stirrer bar and a reflux condenser, 4,4'-dimethoxybenzil(2 g, 0.0075 mmol), aqueous HBr (15 mL, 48%) and glacialacetic acid (15 mL) were placed. The reaction mixture was refluxedfor 24 h, after cooling to room temperature, was poured into100 mL water. Ethyl acetate was added to the mixture to give twophases of which the organic phase containing the product wasseparated and dried over magnesium sulfate for 12 h. The solventwas removed under reduced pressure and the obtained yellowprecipitate was washed thoroughly with water and then dried in avacuum oven at 80 8C. Yield: 94% (1.7 g) and m.p.: 229-231 8C. FTIR(KBr) at cm 1: 3400 (OH phenol), 3045 (C-H aromatic), 1646(C55O), 1576 (C55C), 1223 (C-O). 1H NMR (400 MHz, DMSO-d6,): d6.91-6.95 (d, 4H, J = 8.0 Hz), 7.73-7.77 (d, 4H, J = 8.0 Hz), 10.84 (s,2H). |
94% | With hydrogen bromide; In water; acetic acid; for 24h;Reflux; | Into a 100 mL round-bottomed two-necked flask equipped with a magnetic stir bar and a reflux condenser, 4,4'-dimethoxy benzil (2 g, 0.0075 mol), aqueous HBr (15 mL, 48%) and glacial acetic acid (15 mL) were placed. The reaction mixture was refluxed for 24 h, and then poured in 100 mL water after cooling to room temperature. Ethyl acetate was added to the mixture to give two phases of which the organic phase containing the product was separated and dried over magnesium sulfate for 12 h. The solvent was removed under reduced pressure and the obtained yellow precipitate was washed thoroughly with water and then dried in a vacuum oven at 80 C. Yield: 94% (1.7 g), and melting point: 229-231 C. FT-IR (KBr) at cm-1: 3400 (OH phenol), 3045 (C-H aromatic), 1646 (C=O), 1576 (C=C), 1223 (C-O). 1H NMR (400 MHz, DMSO-d6,): delta 6.91-6.95 (d, 4H, J = 8.0 Hz), 7.73-7.77 (d, 4H, J = 8.0 Hz), 10.84 (s, 2H). |
90% | With hydrogen bromide; acetic acid; for 24h;Reflux; Inert atmosphere; | A mixture of 4,4'-dimethoxybenzil (2.50 g, 0.0092 mol), glacial acetic acid (25 mL), and HBr (30 mL) was refluxed for 12 h under N2. After cooling, 5 mL HBr was added and mixture was refluxed for another 12 h. Upon completion of the reaction (as witnessed by TLC), the medium was poured into 200 mL deionized water. The organic product was extracted with 220 mL ethyl acetate. The organic phase was thoroughly washed with water in order to remove all acids and then dried over magnesium sulfate. The product was obtained as crystal after evaporation of the solvent in a rotary evaporator. The yield after drying in a vacuum oven at 80 C was 90% (1.79 g) with melting point of 120 C. FT-IR (KBr, cm 1): 3031 (OH stretching), 1633 (C55O stretching), 1612 (C55C stretching), 1226 (C-O-C stretching). 1H NMR (400 MHz, DMSO-d6): d = 10.84 (2H OH, s), 6.91-7.77 (8H, m) ppm. C14H10O4: calculated C, 69.42%; H, 4.13%; N, 0%; found C, 69.38%; H, 4.16%; N, 0%. m/e: 242.06, 243.06, 244.06. |
89% | With pyridine hydrochloride; at 180℃; for 48h; | A mixture of 1,2-bis(4-methoxyphenyl)-ethane-1,2-dione prepared according to example 1 (7.275 g, 26.91 mmol) and pyridine hydrochlorate (15.55 g, 134.5 mmol) under an atmosphere of nitrogen is heated to 180 C. for 2 days. After returning to ambient temperature, the mixture is diluted with ethyl acetate and water. The aqueous phase is extracted with ethyl acetate and the recombined organic phases are dried on magnesium sulfate, filtered and concentrated under reduced pressure. The residue is purified by flash chromatography on a silica gel (petroleum ether/ethyl acetate 10/1 to 2/1) to yield 5.789 g (89%) of a white solid. deltaH (300 MHz, MeOH-d) 6.91 (d; J 9.0; 4H), 7.82 (d; J 9.0; 4H). |
80.6% | With hydrogen bromide; acetic acid; at 120℃; for 24h;Inert atmosphere; | Under nitrogen protection, nitrogen is protected. A mixture of 4, 4 -methoxybenzil (2.50g, 0.0092 muM unitunitunitant), 25 ml unitz 40%), unitz 30 ml hydrobromic acid, was added and refluxed 24h under the unitunit_ .sup 120 C. After completion of the reaction, the reaction solution was cooled to room temperature, 200 ml and saturated brine and ethyl acetate were added thereto to extract, and the organic phase, dried over anhydrous magnesium sulfate, concentrated, and then subjected to column chromatography separation and purification. The silica gel uses 300 - 400 mesh silica gel as the stationary phase. The eluate containing the target compound was 1:1 eluted, the solvent was removed under reduced pressure, the solvent was distilled off under reduced pressure, and dried, yielding a yellow powdery intermediate product 2 |
75% | With hydrogen bromide; acetic acid; In water; for 12h;Reflux; | The synthesis of 2 needs two steps. Firstly, a mixture of 1,2-bis(4-methoxyphenyl) ethane-1,2-dione (3 g, 11 m mol), glacial acetic acid (30 ml) and HBr (48%, 100 ml) were added into a three-neck round bottom flask orderly, heated to reflux and stirred for 12 h. Then the mixture was cooled to room temperature and brown precipitation was observed. Then the precipitate was separated by filtration and washed with distilled water three times to give 1,2-bis(4-hydroxyphenyl) ethane-1,2-dione, yield: 75%. Secondly, 1,2-bis(4-hydroxyphenyl) ethane-1,2-dione (2.0 g, 8.2 m mol), 1 - bromine decane (4.04g, 3.78 ml),anhydrous potassium carbonate (2.4g, 0.24 mol) and Tetra-nbutylammoniumbromide (1.33 g, 4.13 m mol) were dissolved in DMF (120 ml). The solution was heated to 120 deg.C and reacted for 90 min. After reaction, the solution was cooled to room temperature, added with water, oscillated by ultrasonic instrument.The cream-color deposit was filtered and washed by distilled water several times to give the target product (2) with a high productivity (about 90%). |
With hydrogen bromide; In acetic acid; for 24h;Reflux; | General Procedure: Dimethoxybenzil in 1:1 48%HBr: HOAc was heated to reflux for 24 h. The reaction mixture was cooled to room temperature, poured into H2O and extracted with EtOAc. The organic phase was washed with H2O, dried (Na2SO4) and concentrated. The residue was purified by column chromatography (silica gel, CH2Cl2: acetone) to afford yellow solids. | |
4 g | With hydrogen bromide; acetic acid; In water; at 70 - 110℃; for 70h; | Synthesis Example 1 Synthesis of 4,4?-dihydroxybenzil (0057) 4,4?-Dimethoxybenzil (5.0 g) was dissolved in acetic acid (95 mL). To the solution, 48 mass % aqueous HBr (31.2 g) was added dropwise at 70 C. over 10 minutes. After addition of HBr, the mixture was stirred at 110 C. for 70 hours. Subsequently, water (150 g) was added to the mixture, to thereby crystallize the product. The crude crystals were recovered through filtration and washed with water (250 g), followed by drying, to thereby yield 4.0 g of 4,4?-dihydroxybenzil as a target product. |
With pyridine hydrochloride; In neat (no solvent); at 180℃; for 14h; | 45 g (0.166 mol) 4 , 4-dimethoxybenzil was mixed with 100 g pyridine hydrochloride (0.865 mol) and the mixture was heated to 180C. The reaction mixture was kept at 180C for 14 hours. The mixture was allowed to cool down and then poured into 500 ml water. The mixture was extracted with 250 ml ethyl acetate. The organic fraction was washed three times with 100 ml brine and dried over MgS04. The solvent was evaporated under reduced pressure and 4,4'- dihydroxybenzil was isolated as a pale yellow powder. (0207) 35.2 g (yield: 87.5 %) of 4 , 4 " -dihydroxybenzil was isolated and used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium persulfate; copper(l) iodide; dimethyl sulfoxide; at 120℃; for 24h; | General procedure: To a stirred solution of alkyne 1 (0.2 mmol) in DMSO (2.0mL) was added CuI (3.8 mg, 0.02 mmol) and Na2S2O8(71.4 mg, 0.3 mmol). The solution was stirred at 140 C for 24 h in the air. After completion, the mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was washed with H2O and dried over MgSO4. After evaporation of the solvent, the residue was purified by preparative thin layer chromatography on silica gel with PE/EtOAc(10/1) as an eluent to give the corresponding 1,2-diketone 2 |
76% | General procedure: In an oven-dried Schlenk tube (25 mL) equipped with a magnetic stir bar was charged with Cu(OAc)2 (10 mol%), Cy-JohnPhos (25 mol%), LiOBut (0.24 mmol), (Bpin)2 (0.3 mmol) and alkyne (1) (0.2 mmol, if the alkyne is solid). The tube was evacuated and backfilled with N2. To this Schlenk tube were added DMF (0.6 mL), 1,4-dioxane (0.9 mL), H2O (0.2 mmol) and alkynes 1 (0.2 mmol, if the alkyne is liquid) by syringe. After stirring for 20 min at room temperature under nitrogen atmosphere, the reaction mixture was flushed with O2. The Schlenk tube was sealed, and the reaction mixture was allowed to stir at room temperature for 48 h. After quenched with aqueous NH4Cl, the aqueous layer was extracted three times with EtOAc. The combined organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography to afford the product (2) (silica gel, EtOAc-PE). The products obtained herein are known compounds, and spectral properties are consistent with literature values | |
62% | With sodium persulfate; zinc(II) iodide; In dimethyl sulfoxide; at 100℃; for 24h;Inert atmosphere; | In a reaction tube, 12.8 mg of zinc iodide, 47.7 mg of 1,2-bis(4-methoxyphenyl)acetylene, 71.4 mg of sodium persulfate and 2.0 mL of dimethylsulfoxide were added under nitrogen atmosphere. Placed in a 100 C oil bath for 24 hours. Conventional treatment gave pure product 33.5 mg, yield 62%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With graphite oxide In chloroform at 100℃; for 24h; | 4.3. Oxidation of cis-stilbenes General procedure: In a typical preparation, a 7.5 mL vial was charged with GO (200 mg), cis-stilbene (50 mg), CHCl3 (0.5 mL) and a magnetic stir bar. The vial was then sealed with a Teflon-lined cap under ambient atmosphere and heated at 100 °C for 24 h. After the reaction was complete, the mixture was cooled to room temperature and washed with CH2Cl2 (50 mL). The filtrate was collected and the solvent was evaporated to obtain the crude product, which was then purified by silica chromatography (CH2Cl2 or CH2Cl2/hexanes as the eluent) and the solvent was removed under reduced pressure to obtain the desired product. All isolated products matched spectroscopic data reported previously in the literature (see ESI). |
With iodine In dimethyl sulfoxide at 155℃; for 10h; | ||
With selenium(IV) oxide; sulfuric acid; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With ammonium acetate; acetic acid at 180℃; for 0.0833333h; microwave irradiation; | |
97% | With ammonium acetate In ethanol at 40℃; for 0.583333h; Sonication; Green chemistry; | 2.4. General procedure for the synthesis of 2,4,5-trisubstituted imidazoles ultrasonic irradiation General procedure: A 25 mL Erlenmeyer flask was charged with benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (0.4 g, 5 mmol), SA-MNPs (0.1 g) and ethanol (10 mL). The reaction flask was located in the ultrasonic bath, where the surface of reactants is slightly lower than the level of the water, and irradiated under 20, 40, 60, 80 and 100% of the power of the ultrasonic bath and the temperature inside the reactor at 40 °C for the period of time (The reaction was monitored by TLC) separately as indicated in Table 4. After the reaction was completed, the catalyst was separated by an external magnet and reused as such for the next experiment. The reaction mixture was concentrated on a rotary evaporator under reduced pressure and the solid product obtained was dissolved in acetone and filtered. The solid product obtained was washed with water and recrystallized from acetone-water 9:1 (v/v) to offer pure product 3a in 98% yield. All products were known and characterized by comparison of their physical and spectra data with those already reported [31]. |
95% | With ammonium acetate In ethanol for 3h; Reflux; Green chemistry; |
90% | With ammonium acetate at 130℃; for 1.33333h; Neat (no solvent); | |
90% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; | |
90% | With trimethylsilyl trifluoromethanesulfonate; 1,1,1,3,3,3-hexamethyl-disilazane In neat (no solvent) at 150℃; for 0.5h; Microwave irradiation; | |
85% | With lithium tetrafluoroborate; ammonium acetate at 120℃; for 1h; Neat (no solvent); | |
78% | With ammonium acetate In ethanol at 78℃; Green chemistry; | General procedure General procedure: A mixture of 1,2-diketone (0.5 mmol), aldehyde (0.5 mmol),ammonium acetate (1.5 mmol) and Fe3O4g-C3N4 (20 mg)in ethanol (1 mL) was heated at 78 °C with stirring for120-200 min. After the completion of the reaction, ethanolwas added and the Fe3O4g-C3N4 was separated magneticallyusing a bar magnet. The reaction mixture was allowedto cool to room temperature to recrystallize from ethanolto get the pure final product. All compounds were knownand characterized on the basis of their melting point and bycomparison with those reported in the literature. |
77% | With ammonium acetate at 20℃; | |
29% | With ammonium metavanadate; ammonium acetate In methanol for 24h; Reflux; | General Procedure for the Preparation of Compounds4a-d To benzoins (3a-d) (1 mmol), benzaldehyde (1 mmol),ammonium acetate (100 mg), and ammonium vanadate (100mg) in methanol (100 mL) were added and the mixture wasrefluxed for 24 h. The progress of the reaction was followedby TLC. After completion of the reaction, the solvent wasremoved under reduced pressure. Water (50 ml) and ethylacetate (100 ml) were added and well mixed. The organicphase was separated and was dried over sodium sulphate.The solvent was filtered and removed under reduced pressure.The residue was purified by column chromatographyusing hexane and ethyl acetate as mobile phase. |
With ammonium acetate In acetic acid Heating; | ||
With ammonium acetate; acetic acid Reflux; | ||
25 %Spectr. | Stage #1: benzaldehyde; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With titanium(IV); ammonium acetate at 100℃; for 1h; Molecular sieve; Stage #2: In toluene at 100℃; for 10h; Molecular sieve; | General Procedure for the One-Pot Synthesis of 2,4,5-Triaryl-1H-imidazoles General procedure: A mixture of benzil (1 mmol, 0.21 g), aldehyde (1 mmol), ammonium acetate (2.2 mmol, 0.17 g), and Ti4+/4A (0.1 g) wasstirred in a 10 mL flask at 100 °C. After 1 h toluene (1 mL) was added because the precipitated product impeded stirring of the melt. The stirring was continued, and progress of the reaction was monitored by TLC. After completion (10 h), the mixture was cooled to room temperature, diluted with acetone (10 mL), any solid was filtered off, and the filtrate was evaporated. The product was purified by recrystallization from ethanol. A mixture of benzil (1 mmol, 0.21 g), aldehyde (1 mmol), ammonium acetate (2.2 mmol, 0.17 g), and Ti4+/4A (0.1 g) was stirred in a 10 mL flask at 100 °C. After 1 h toluene (1 mL) was added because the precipitated product impeded stirring of the melt. The stirring was continued, and progress of the reaction was monitored by TLC. After completion (10 h), the mixture was cooled to room temperature, diluted with acetone (10 mL), anysolid was filtered off, and the filtrate was evaporated. Theproduct was purified by recrystallization from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 80℃; for 0.0833333h; | |
88% | In ethanol for 0.5h; Heating; | |
88% | With iodine In acetonitrile at 60℃; for 6h; | Synthesis of 2,3-dihydro-pyrazines 2; general procedure General procedure: I2 (2.5 mg, 0.01 mmol) was added to a stirred solution of 1,2-diketone1 (0.1 mmol) and ethylenediamine (0.15 mmol) in CH3CN (1.0 mL).The solution was stirred at 60 oC in air until all the starting materialwas consumed. The mixture was cooled to room temperature. Afterevaporation of the solvent, the residue was purified by preparative thinlayerchromatography on silica gel with petroleum ether/EtOAc (10/1) asan eluent to give the corresponding 2,3-dihydro-pyrazine 2. |
75% | In diethyl ether for 0.5h; Heating; | |
40% | With ziconium(IV) oxychloride octahydrate In ethanol at 25℃; for 0.25h; | |
0.247 g | With dihydrogen peroxide In ethanol for 0.5h; Reflux; | A general procedure for preparation of dihydropyrazines 3 General procedure: 2-hydroxy-1,2-diphenylethanone 1a (0.2123 g, 1 mmol) and YbCl3 (0.0279 g, 0.1 mmol) were dissolved in 5mL EtOH and stirred until the solid dissolved completely in refluxing, then ethylenediamine 2a (0.10 mL, 1.5 mmol) and H2O2 (0.0224 g, 0.2 mmol) was added into the reaction mixture. After 30min, TLC showed the reaction to be complete. The reaction mixture was cooled to r.t., and then evaporated in vacuum. The product purified by column chromatography on neutral alumina deactivated with H2O (6 wt%) (PE-EtOAc= 5:1) to give pale yellow solid 3a (0.2271 g, 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.8% | In hydrogenchloride for 1h; heating on boiling water bath; | |
97% | In deoxygenated acetic acid | 2 2,3-bis(4-Methoxyphenyl)quinoxaline-6-carboxylic Acid EXAMPLE 2 2,3-bis(4-Methoxyphenyl)quinoxaline-6-carboxylic Acid Into a 500 mL three-necked, round-bottomed flask equipped with a magnetic stirrer, a nitrogen inlet, and a condenser, 3,4-diaminobenzoic acid (14.21 g, 93.4 mmol) was dissolved in deoxygenated acetic acid (250 mL). 4,4'-Dimethoxybenzil (25,0 g, 92.5 mmol) was then added to the resulting brown and clear mixture at room temperature. The reaction mixture was heated under reflux with vigorous stirring for 8 h. After having been allowed to cool down to room temperature, the brown mixture was poured into distilled water. The resulting light brown precipitates were collected by suction filtration and then air-dried overnight. It was recrystallized from ethanol to give 34.8 g (97% yield) of yellow solid, m.p. 296-298° C. Anal. Calcd. for C23H18N2O4: C, 71.49%; H, 4.70%; N, 7.25%: Found: C, 71.51%; H, 4.55%; N, 7.11%. FT-IR (KBr, cm-1): 1693 (carbonyl), 2838 (methyl). Mass spectrum (m/e): 386 (M+, 100% relative abundance). 1H-NMR (DMSO-d6, δ in ppm): 3.80 (s, 6H, OCH3), 6.92-6.96 (d, 4H, Ar), 7.44-7.48 (dd, 8.8.11-8.14 (d, 1H, Ar), 8.22-8.26 (dd, 1H, Ar), 8.58-8.59 (d, 1H, Ar), 13.49 (s, 1H, COOH). 13C-NMR (DMSO-d6, δ in ppm): 55.12, 113.52, 128.90, 128.98, 130.48, 130.74, 131.06, 131.17, 131.49, 139.38, 142.08, 153.46, 154.06, 159.85, 159.97, 166.59. |
44% | With acetic acid In sodium hydroxide | 1 6.1. Example 1 Compound 129: 2,3-bis-(4-Methoxyphenyl)quinoxaline-6-carboxylic acid A mixture of 3,4-diaminobenzoic acid (0.153 g, 1.00 mmol), 4,4'-dimethoxybenzil (0.271 g, 1.00 mmol) and acetic acid (6 mL) was stirred at reflux for 12 h, cooled to room temperature and poured into water (75 mL). The resultant solid was taken up in aqueous sodium hydroxide (2M) and washed with dichloromethane; the aqueous layer was acidified and the resultant solid was recrystallized from methanol to afford 2,3-bis-(4-methoxyphenyl)quinoxaline-6-carboxylic acid (0.171 g, 44% yield) as a yellow solid: mp 284-285° C.; 1H NMR (500 MHz, Acetone-d6) δ 8.79 (s, 1H), 8.39 (d, 1H), 8.21 (d, 1H), 7.61 (d, 4H), 6.97 (d, 4H), 3.89 (s, 7H); ESI MS m/z 387 [C23H18N2O4+H]+. |
44% | With acetic acid In sodium hydroxide | 2 6.2. Example 2 Synthesis of Compound 129: 2,3-bis-(4-Methoxyphenyl) quinoxaline-6-carboxylic acid A mixture of 3,4-diaminobenzoic acid (0.153 g, 1.00 mmol), 4,4'-dimethoxybenzil (0.271 g, 1.00 mmol) and acetic acid (6 mL) was stirred at reflux for 12 h, cooled to room temperature and poured into water (75 mL). The resultant solid was taken up in aqueous sodium hydroxide (2M) and washed with dichloromethane; the aqueous layer was acidified and the resultant solid was recrystallized from methanol to afford 2,3-bis-(4-methoxyphenyl)quinoxaline-6-carboxylic acid (0.171 g, 44% yield) as a yellow solid: mp 284-285° C.; 1H NMR (500 MHz, Acetone-d6) 8.79 (s, 1H), 8.39 (d, 1H), 8.21 (d, 1H), 7.61 (d, 4H), 6.97 (d, 4H), 3.89 (s, 7H); ESI MS m/z 387 [C23H18N2O4+H]+. |
With acetic acid for 8h; Heating; | ||
In ethanol for 24h; Reflux; | General procedure for the synthesis of 2,3-Bis(aryl)quinoxaline-6-carboxylic acid and 2,3-Bis(aryl)quinoxaline: General Procedure: A mixture of 1,2-diketone and 3,4-diaminobenzoic acid or 1,2-phenylenediamine (1.1 equiv.) in EtOH was heated to reflux for 24 h. The reaction mixture was cooled to room temperature and poured into 1: 5 concentrated HCl: H2O. The precipitates were collected by vacuum filtration, washed with H2O, and dried under high vacuum overnight. | |
With acetic acid for 12h; Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium In ethanol for 8h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With acetic acid; for 3.0h;Reflux; | A solution of 1,2-bis(4-methoxyphenyl)ethane-1,2-dione (270 mg, 1.00 mmol, 1.00 equiv) and <strong>[603-81-6]2,3-<strong>[603-81-6]diaminobenzoic acid</strong></strong> (152 mg, 1.00 mmol, 1.00 equiv) in acetic acid (10 mL) was heated under reflux for 3 h. The reaction was quenched by the addition of 20 mL of ice/water. The solids were collected by filtration and purified by re-crystallization from methanol, affording 100 mg (26%) of 2,3-bis(4-methoxyphenyl)quinoxaline-5-carboxylic acid as a yellow solid. LC-MS-PH (ES, m/z): [M+H]+ calculated for C23H19N2O4: 387. Found: 387. 1H-NMR (300 MHz, DMSO, ppm): delta 14.605 (s, 1H), 8.422-8.358 (m, 2H), 8.002-7.963 (m, 1H), 7.520-7.492 (m, 4H), 7.033-6.972 (m, 4H), 3.819-3.808 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With selenium(IV) oxide; In dimethyl sulfoxide; at 170℃; for 0.0166667h;Microwave irradiation; | General procedure: Selenium dioxide (1.5 mmol) was added into a solutionof ethanone derivatives 11 (1 mmol) in DMSO (1.5 mL) andirradiated in the microwave oven for 1 min at 170C. The hotmixture was filtered to remove the selenium metal and thefiltrate was purified by column chromatography in silica gelusing EtOAc/hexanes 7:3 as eluent. |
88% | With water; copper(ll) bromide; In dichloromethane; ethyl acetate; for 18h;Reflux; Inert atmosphere; | General procedure: Copper(II) bromide (CuBr2, 268 mg, 1.2 mmol) was added to a solution of skeleton 5 (1.0 mmol) in the co-solvent of EtOAc and CH2Cl2 (1:1, 20 mL), at 25 C. The reaction mixture was stirred at reflux for 18 h. The reaction mixture was cooled to 25 C. Saturated NaHCO3 (5 mL) was added to the reaction mixture and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product. Purification on silica gel (hexanes/EtOAc = 10/1-6/1) afforded skeletons 3 and 6. |
76% | Step 3. 1,2-Bis(4-methoxyphenyl)ethane-1,2-dione To a solution of <strong>[120-44-5]1,2-bis(4-methoxyphenyl)ethan-1-one</strong> (1 g, 3.90 mmol) in DMSO (20 mL) was added SeO2 (1.76 g, 15.86 mmol) in several batches at 100 C. over 30 min, and then stirred for 3 hr at this temperature. The reaction was quenched by the addition of water (200 mL) and extracted with dichloromethane (3×50 mL), dried over magnesium sulfate and concentrated in vacuo to give a residue, which was purified by silica gel column chromatography (1%10% ethyl acetate in petroleum ether) to afford 1,2-bis(4-methoxyphenyl)ethane-1,2-dione as a brown solid (600 mg, 76%).(ES, m/z): [M+H]+ 270.01H-NMR (300 MHz, CDCl3) delta 7.94-7.99 (m, 4H), 6.96-7.02 (m, 4H), 3.90 (s, 6H) |
With iodine; dimethyl sulfoxide; copper(II) oxide; at 100℃; for 4h; | General procedure: A stirred solution of deoxybenzoin 1a (196 mg, 1.0 mmol), CuO (88 mg, 1.1 mmol), and iodine (279 mg, 1.1 mmol) was heated at 100 C for 4 h in DMSO (3 mL), after the disappearance of the starting material (TLC), 1,2-diamine 2a (324 mg, 3.0 mmol) was added and stirred for another 1 h. Then the reaction mixture was poured into 50 mL brine and the aqueous layer was extracted with EtOAc (3×50 mL). The extract was washed with Na2S2O3 solution, dried over anhydrous Na2SO4 then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether/EtOAc as the eluent to give the expected products 3aa as the yellow solid (240 mg, 85% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With ammonium acetate In acetic acid at 120℃; | 2.2 General procedure for the synthesis naphthaleneincorporated 2,4,5-trisubstituted imidazoles (2a-2l) General procedure: A mixture of naphthaldehyde (10 mmol), substituted benzil(10 mmol) and ammonium acetate (50 mmol) were dissolvedin acetic acid in two necked 100 mL round bottom flask. Thereaction mixture was refluxed for 12-14 h. The completionof reaction was monitored by TLC using petroleum ether andethyl acetate (3:1) as eluent. After completion of the reaction,the mixture was poured into ice cold water. The solid compound precipitated was filtered and dried. All the crudeproducts were purified by column chromatography except 2a,2b, 2c, 2d and 2h, which purified by recrystallization usingethanol. |
With ammonium acetate; acetic acid Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With acetic acid In ethanol Reflux; | |
95% | With zirconium(IV) chloride In methanol at 20℃; for 4h; | |
95% | With SBA-15 mesoporous silica supported Fe(III)-Schiff base In water for 2h; Reflux; |
94% | With silica-supported stannous chloride In methanol at 20℃; for 3h; | |
94% | With zirconium oxide salicylaldehyde-(3-aminopropyl)trimethoxysilane imine complex modified SBA-15 In water for 5h; Reflux; | |
93% | With Cu(II)-Schiff base/SBA-15 In water for 2h; Reflux; | General procedure for the synthesis of pyrido[2,3-b]pyrazines, pyrido[3,4-b]pyrazines and 2,3-disubstituted quinoxalines in water General procedure: A round-bottomed flask equipped with a magnet and condenser was charged with desired 1,2-diamine (1.0 mmol), 1,2-diketone (1.0 mmol), water (2 mL) and catalyst Cu/SBA-15 (0.01 g (0.0014 mmol)). The resulting mixture was stirred at reflux temperature for the appropriate times, and the course of the reaction was monitored using TLC on silica gel. For separation of the catalyst, the reaction mixture (at the end of reaction) was filtered and the precipitates on the filter were dissolved in ethanol or ethyl acetate. These solvents can dissolve the products (and also organic starting materials), but the catalyst was remained insoluble. After filtration of the later solution, the catalyst was recovered |
88% | With ziconium(IV) oxychloride octahydrate In water at 100℃; for 3h; Green chemistry; | 3 4.2. General procedure for the synthesis of compounds 3a-3p For the synthesis of entitled heterocycles, a roundbottom flask equipped with a stir bar was chargedwith 1,2-phenylenediamine (1.0 mmol), 1,2-diketones(1.0 mmol), water (2 mL) and zirconium(IV) oxide chloride(25 mol%). The resulting mixture was heated in an oil bathat 100 8C for the appropriate time, and the course of the reaction was monitored using TLC on silica gel. Finally, thereaction mixture was cooled and the crude mixture waspurified by column chromatography or crystallization togive the desired product. The authenticity of the productswas established by comparing their melting points withdata of the literature and by analyzing the spectroscopicdata of 1H and 13C NMR and IR [9-16,26,27]. |
87% | With silica-supported bismuth(III) chloride In methanol at 20℃; for 3h; | 4.1 2.3 General procedure for the acid-catalyzed benzo[N,N]-heterocyclic condensation General procedure: A mixture of arene-1,2-diamine (1.2mmol), 1,2-dicarbonyl (1mmol), and 0.20g of BiCl3/SiO2 (5mol %) was taken in methanol (5mL) and stirred at room temperature for the appropriate reaction time (Scheme 1). After completion of the reaction (monitored by TLC using ethyl acetate/hexane (2:8 v/v) or GC), dichloromethane was added to the reaction mixture and the catalyst was recovered by filtration. The organic medium was removed with rotary evaporator under reduced pressure. The crude products were purified by column chromatography using ethyl acetate/hexane (2:8 v/v) [dichloromethane/ethanol (9:1 v/v) for products 1h-1m] to afford pure products for analytical measurements. The products were identified by comparison of their NMR and mass spectra with authentic samples. |
77% | With mesoporous silica SBA-15 functionalized with Cu(II)-DiAmSar complex In neat (no solvent) at 100℃; for 1.5h; | 2.3. General procedure for the synthesis of pyrazine-basedheterocycles under solvent-free conditions General procedure: A round-bottomed flask equipped with a magnet and condenserwas charged with the desired 1,2-diamine (1.0 mmol),1,2-diketone (1.0 mmol), and catalyst (Cu(II)DiAmSar/SBA-15,0.005 g). The resulting mixture was heated at 100 °C for theappropriate time. The course of the reaction was monitoredusing TLC on silica gel. Finally, the reaction mixture was cooled,and the crude mixture was purified by column chromatographyor crystallization to get the desired product. Spectral and physicaldata for all heterocycles were compared with referencesamples and were in accord with previously reported data. |
76% | With 5-sulfosalicylic acid anchored to silica-modified Fe3O4 nanocomposite In ethanol at 60℃; | General procedure for the synthesis of quinoxaline derivatives General procedure: To a mixture of a 1,2-diketone (1.0 mmol) and 1,2-diaminobenzene (1.0 mmol) in ethanol (2.0 mL), Fe3O4(at)SiO2(at)5-SA (20 mg) was added and the mixture was stirred at 60 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, the magnetic catalyst was separated by an external magnet. The products were purified by recrystallization from ethanol or methanol. |
22% | In methanol for 1h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With zirconium oxide salicylaldehyde-(3-aminopropyl)trimethoxysilane imine complex modified SBA-15 In water for 5h; Reflux; | |
95% | With SBA-15 mesoporous silica supported Fe(III)-Schiff base In water for 2h; Reflux; | |
94% | With Cu(II)-Schiff base/SBA-15 In water for 2h; Reflux; | General procedure for the synthesis of pyrido[2,3-b]pyrazines, pyrido[3,4-b]pyrazines and 2,3-disubstituted quinoxalines in water General procedure: A round-bottomed flask equipped with a magnet and condenser was charged with desired 1,2-diamine (1.0 mmol), 1,2-diketone (1.0 mmol), water (2 mL) and catalyst Cu/SBA-15 (0.01 g (0.0014 mmol)). The resulting mixture was stirred at reflux temperature for the appropriate times, and the course of the reaction was monitored using TLC on silica gel. For separation of the catalyst, the reaction mixture (at the end of reaction) was filtered and the precipitates on the filter were dissolved in ethanol or ethyl acetate. These solvents can dissolve the products (and also organic starting materials), but the catalyst was remained insoluble. After filtration of the later solution, the catalyst was recovered |
86% | With ziconium(IV) oxychloride octahydrate In water at 100℃; for 3h; Green chemistry; | 5 4.2. General procedure for the synthesis of compounds 3a-3p For the synthesis of entitled heterocycles, a roundbottom flask equipped with a stir bar was chargedwith 1,2-phenylenediamine (1.0 mmol), 1,2-diketones(1.0 mmol), water (2 mL) and zirconium(IV) oxide chloride(25 mol%). The resulting mixture was heated in an oil bathat 100 8C for the appropriate time, and the course of the reaction was monitored using TLC on silica gel. Finally, thereaction mixture was cooled and the crude mixture waspurified by column chromatography or crystallization togive the desired product. The authenticity of the productswas established by comparing their melting points withdata of the literature and by analyzing the spectroscopicdata of 1H and 13C NMR and IR [9-16,26,27]. |
75% | In 1,4-dioxane Reflux; | |
74% | With mesoporous silica SBA-15 functionalized with Cu(II)-DiAmSar complex In neat (no solvent) at 100℃; for 1.5h; | 2.3. General procedure for the synthesis of pyrazine-basedheterocycles under solvent-free conditions General procedure: A round-bottomed flask equipped with a magnet and condenserwas charged with the desired 1,2-diamine (1.0 mmol),1,2-diketone (1.0 mmol), and catalyst (Cu(II)DiAmSar/SBA-15,0.005 g). The resulting mixture was heated at 100 °C for theappropriate time. The course of the reaction was monitoredusing TLC on silica gel. Finally, the reaction mixture was cooled,and the crude mixture was purified by column chromatographyor crystallization to get the desired product. Spectral and physicaldata for all heterocycles were compared with referencesamples and were in accord with previously reported data. |
25% | In methanol for 1h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With acetic acid; In ethanol; for 24h;Schlenk technique; Inert atmosphere; Reflux; | General procedure: To a stirred solution of benzil (322 mg, 1.6 mmol) in ethanol(15 mL) was added <strong>[771-97-1]2,3-diaminonaphthalene</strong> (250 mg, 1.6 mmol)and acetic acid (0.5 mL). The reaction mixture was heated at refluxunder a nitrogen atmosphere for 24 h. The reaction mixture wascooled to room temperature and a precipitate collected by filtration to give L1 as a brown solid (0.34 g, 64%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | at 75℃; for 1h; | |
100% | With zirconium(IV) chloride In methanol at 20℃; for 0.5h; | |
99% | With Cs(cetyltrimethylammonium)<SUB>2</SUB>PW<SUB>12</SUB>O<SUB>40</SUB> In neat (no solvent) at 80℃; for 2.25h; Green chemistry; | 2.3. General method for the preparation of quinoxalinederivatives A mixture of 1,2-dicarbonyl (1 mmol) and 1,2-diamine(1 mmol) derivatives in the presence of an appropriateamount of the Cs(CTA)2PW12O40 catalyst was stirred at agiven temperature. The progress of the reaction wasmonitored by thin layer chromatography (TLC). Aftercompletion of the reaction, 5 mL of hot ethanol was addedto the reaction mixture and the solid catalyst was filtered.The pure products were obtained after crystallizationand analyzed without any further purification. All ofthe obtained quinoxalines are known compounds andidentified by 1H NMR and melting points compared withthe literature values. The melting points, spectral (1H NMR)and elemental analysis data for the products are givenbelow. |
98% | In acetic acid at 20℃; for 0.333333h; | |
98% | With ZnO-β-zeolite In ethanol at 20℃; for 0.15h; | |
98% | With silica-supported stannous chloride In methanol at 20℃; for 0.5h; | |
98% | With vitamin B1 In methanol at 25℃; for 0.416667h; Sonication; | |
98% | With zirconium oxide salicylaldehyde-(3-aminopropyl)trimethoxysilane imine complex modified SBA-15 In water for 3h; Reflux; | |
98% | With silica-supported bismuth(III) chloride In methanol at 20℃; for 0.5h; | 4.1 2.3 General procedure for the acid-catalyzed benzo[N,N]-heterocyclic condensation General procedure: A mixture of arene-1,2-diamine (1.2mmol), 1,2-dicarbonyl (1mmol), and 0.20g of BiCl3/SiO2 (5mol %) was taken in methanol (5mL) and stirred at room temperature for the appropriate reaction time (Scheme 1). After completion of the reaction (monitored by TLC using ethyl acetate/hexane (2:8 v/v) or GC), dichloromethane was added to the reaction mixture and the catalyst was recovered by filtration. The organic medium was removed with rotary evaporator under reduced pressure. The crude products were purified by column chromatography using ethyl acetate/hexane (2:8 v/v) [dichloromethane/ethanol (9:1 v/v) for products 1h-1m] to afford pure products for analytical measurements. The products were identified by comparison of their NMR and mass spectra with authentic samples. |
98% | With SBA-15 mesoporous silica supported Fe(III)-Schiff base In water for 0.5h; Reflux; | |
97% | With potassium hydrogensulfate In ethanol at 20℃; for 0.2h; | |
97% | With polyaniline/SiO2 In ethanol at 20℃; for 0.3h; | |
97% | With Cu(II)-Schiff base/SBA-15 In water for 20.5h; Reflux; | General procedure for the synthesis of pyrido[2,3-b]pyrazines, pyrido[3,4-b]pyrazines and 2,3-disubstituted quinoxalines in water General procedure: A round-bottomed flask equipped with a magnet and condenser was charged with desired 1,2-diamine (1.0 mmol), 1,2-diketone (1.0 mmol), water (2 mL) and catalyst Cu/SBA-15 (0.01 g (0.0014 mmol)). The resulting mixture was stirred at reflux temperature for the appropriate times, and the course of the reaction was monitored using TLC on silica gel. For separation of the catalyst, the reaction mixture (at the end of reaction) was filtered and the precipitates on the filter were dissolved in ethanol or ethyl acetate. These solvents can dissolve the products (and also organic starting materials), but the catalyst was remained insoluble. After filtration of the later solution, the catalyst was recovered |
97% | With C20H24Cl2N2O2Zr In ethanol at 20℃; for 0.583333h; Green chemistry; | |
96% | With titanium(IV) oxide In 1,2-dichloro-ethane at 25℃; for 1h; | |
96% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With zirconium dioxide In ethanol at 25℃; for 0.0333333h; Stage #2: 1,2-diamino-benzene In ethanol at 60℃; for 0.1h; | |
96% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In ethyl acetate at 0 - 20℃; for 5h; | |
95% | With aluminum oxide at 80℃; for 0.416667h; Neat (no solvent); | |
95% | With ziconium(IV) oxychloride octahydrate In ethanol at 25℃; for 0.25h; | |
95% | With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 80℃; for 0.0833333h; | |
95% | With α-molybdenum trioxide In ethanol at 25 - 60℃; for 0.166667h; Green chemistry; | |
95% | In neat (no solvent) at 20℃; for 0.25h; Green chemistry; | General procedure for the synthesis of quinoxalines under solventless conditions General procedure: A mixture of 1,2-phenylenediamine derivative (1 mmol), 1,2-diketones (1 mmol) and nano SbCl5.SiO2 (62%w/w ) (0.15 g) was stirred at room temperature under solventless condition. The reaction was monitored by TLC (n-hexane:ethyl acetate, 7:3). After completion of the reaction, the mixture was washed with chloroform (2×5 mL) and filtered to recover the catalyst. The solvent was evaporated and the crude product was recrystallized from ethanol (5 mL) to afford pure quinoxaline derivatives. |
95% | With 2-methylenesuccinic acid In water at 20℃; for 1h; Schlenk technique; Green chemistry; | |
94% | In acetonitrile at 25℃; for 0.05h; | |
94% | With toluene-4-sulfonic acid In methanol at 25℃; for 0.0833333h; | |
94% | With aluminum oxide at 20℃; for 0.166667h; neat (no solvent); | |
94% | With nano-BF3*SiO2 at 20℃; for 0.133333h; Neat (no solvent); | |
94% | With rice husk In water; acetonitrile at 50℃; for 0.666667h; Green chemistry; | General procedure for the synthesis of quinoxaline derivatives General procedure: A mixture of 1,2-dicarbonyl compound (1 mmol), o-phenylenediamine (1 mmol) and RiH (0.35 mol %) in H2O/CH3CN (2 mL/2 mL) was stirred at 50 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, and evaporation of the solvents, the reaction solid product was extracted with Et2O (3 × 15 mL). The catalyst was filtered and reused for further runs. Et2O was evaporated and the solid residue recrystallized with ethanol to afford the pure product. The physical and spectral data of the known compounds were in agreement with those reported in the literature [40,43,58,59]. |
94% | With 1-(propyl-3-sulfonate) 3-methylimidazol(3H)-1-ium phosphotungstate In water at 20℃; for 0.3h; | |
94% | With acetic acid In ethanol at 22 - 25℃; for 1h; Irradiation; | 4.13. General experimental procedure for the synthesis of 2,3-diarylquinoxalines 5c-5k General procedure: A mixture of 1,2-diketone (1.0 mmol), 1,2-diamine (1.0 mmol), and absolute ethanol (4 mL) or absolute ethanol/acetic acid (4 mL/0.4 mL) was irradiated under ultrasound in an open glass at room temperature (22-25 °C) until completion of the reaction. The progress of the reaction was monitored by TLC. After the reaction was completed, the mixture was concentrated under vacuum, and the residue was purified by a flash chromatography column in silicagel using EtOAc:hexane (7:3) as the eluent to provide the desired product 5. |
94% | With acetic acid In ethanol at 22 - 25℃; for 1h; Sonication; | General experimental procedure for the synthesis of 2,3-diarylquinoxalines 5c-5k General procedure: A mixture of 1,2-diketone (1.0 mmol), 1,2-diamine (1.0 mmol),and absolute ethanol (4 mL) or absolute ethanol/acetic acid (4 mL/0.4 mL) was irradiated under ultrasound in an open glass at room temperature (22-25 C°) until completion of the reaction. The progress of the reaction was monitored by TLC. After the reaction was completed, the mixture was concentrated under vacuum, and the residue was purified by a flash chromatography column in silica gel using EtOAc:hexane (7:3) as the eluent to provide the desired product 5. |
94% | With H3PMo12O40 nanoparticles immobilized on imidazole functionalized core-shell Fe3O4(at)SiO2 nanoparticle In ethanol at 20℃; for 0.25h; Green chemistry; | 5.1 2.2.4. General procedure for the preparation of quinoxaline derivatives General procedure: To a stirred solution of amine (1 mmol) and carbonyl compounds (1 mmol) in EtOH (5 mL) were added Fe3O4SiO2-imid-PMAn (0.03 g, 0.5 mol%). The progress of the reaction was followed by thin-layer chromatography (TLC). After completion of the reaction, ethyl acetate was added to the solidified mixture and the insoluble catalyst was separated by magnetic field. The filtrate was dried and organic medium was removed with a rotary evaporator under reduced pressure. The crude products were crystallized from ethanol to afford pure products for analytical measurements. |
94% | With acetic acid In ethanol at 22 - 25℃; for 1h; Irradiation; | 4.2.3. Experimental Procedure for 2,3-diarylquinoxalines(8) General procedure: A mixture of 1,2-diketone 12 (0.5 mmol), 1,2-diamine(0.5 mmol) and absolute ethanol (2 mL) or absolute ethanol/acetic acid (2 mL/0.2 mL) was irradiated under ultrasoundin an open glass at room temperature (22-25 C) untilcompletion of the reaction. The progress of the reaction wasmonitored by TLC. After the reaction was completed, themixture was concentrated in vacuum and the residue waspurified by flash chromatography column in silica gel usingEtOAc/hexanes 7:3 as eluent to give the desired product 8. |
94% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With ZrOL2(at)SMNP In ethanol at 25℃; for 0.0333333h; Stage #2: 1,2-diamino-benzene In ethanol at 60℃; for 0.333333h; | General procedure for the synthesis of quinoxalines and pyrido pyrazines General procedure: A mixture of the required 1,2-dicarbonyl (1 mmol) and ZrOL2&SMNP (0.004 g) in ethanol (0.5 ml) was stirred at 25°C for 2 min. Then, the required 1,2-diamine (1.5 mmol) was added to the mixture, which was stirred at 60 °C for the appropriate reaction time. The progress of the reaction was monitored by TLC or GC. After completion of the reaction, the precipitate was dissolved by adding ethanol, and ZrOL2&SMNP was separated by decantation of the reaction mixture in the presence of an external magnet. Most of the product was precipitated purely by concentrating and cooling the ethanolic solution. There maining product was isolated from an excess of 1,2-diamine by plate chromatography eluted with n-hexane-EtOAc (10/2). Structural assignments of the products were based on their 1H and 13C NMR spectra. |
94% | With acetic acid In ethanol for 1h; | |
93% | With manganese(ll) chloride In ethanol at 20℃; for 0.25h; | |
93% | With zirconium tetrakis(dodecyl sulfate) In water at 20℃; for 0.583333h; | |
93% | With Fe/Al-MCM-41 In acetonitrile for 0.166667h; Reflux; | |
93% | With Thiamine hydrochloride In ethanol at 20℃; for 0.2h; | |
92% | In dimethyl sulfoxide at 20℃; for 0.666667h; | |
92% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate In water at 20℃; for 0.5h; | |
92% | With iodine | |
92% | With ziconium(IV) oxychloride octahydrate In water at 100℃; for 2h; Green chemistry; | 14 4.2. General procedure for the synthesis of compounds 3a-3p For the synthesis of entitled heterocycles, a roundbottom flask equipped with a stir bar was chargedwith 1,2-phenylenediamine (1.0 mmol), 1,2-diketones(1.0 mmol), water (2 mL) and zirconium(IV) oxide chloride(25 mol%). The resulting mixture was heated in an oil bathat 100 8C for the appropriate time, and the course of the reaction was monitored using TLC on silica gel. Finally, thereaction mixture was cooled and the crude mixture waspurified by column chromatography or crystallization togive the desired product. The authenticity of the productswas established by comparing their melting points withdata of the literature and by analyzing the spectroscopicdata of 1H and 13C NMR and IR [9-16,26,27]. |
92% | With mesoporous silica SBA-15 functionalized with Cu(II)-DiAmSar complex In neat (no solvent) at 100℃; for 0.166667h; | 2.3. General procedure for the synthesis of pyrazine-basedheterocycles under solvent-free conditions General procedure: A round-bottomed flask equipped with a magnet and condenserwas charged with the desired 1,2-diamine (1.0 mmol),1,2-diketone (1.0 mmol), and catalyst (Cu(II)DiAmSar/SBA-15,0.005 g). The resulting mixture was heated at 100 °C for theappropriate time. The course of the reaction was monitoredusing TLC on silica gel. Finally, the reaction mixture was cooled,and the crude mixture was purified by column chromatographyor crystallization to get the desired product. Spectral and physicaldata for all heterocycles were compared with referencesamples and were in accord with previously reported data. |
92% | With 5-sulfosalicylic acid anchored to silica-modified Fe3O4 nanocomposite In ethanol at 60℃; | General procedure for the synthesis of quinoxaline derivatives General procedure: To a mixture of a 1,2-diketone (1.0 mmol) and 1,2-diaminobenzene (1.0 mmol) in ethanol (2.0 mL), Fe3O4(at)SiO2(at)5-SA (20 mg) was added and the mixture was stirred at 60 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, the magnetic catalyst was separated by an external magnet. The products were purified by recrystallization from ethanol or methanol. |
91% | With 1-butylimidazolium tetrafluoroborate at 20℃; for 0.333333h; | |
91% | In ethanol Reflux; | |
91% | With nitrilo-tris(methylenephosphonic acid) In ethanol; water at 20℃; for 0.266667h; Green chemistry; | General Experimental Procedure for the Synthesis of Quinoxaline Derivatives General procedure: A mixture of 1,2-diamines (1 mmol) and 1,2-dicarbonyls (1 mmol) in ethanol (3 mL)was poured to the solution of NTMPA (5 mol%, 15 mg) in distilled water (3 mL) atroom temperature. The reaction was monitored by thin-layer chromatography (TLC). Aftercompletion of the reaction, water (10 mL) was added, and the mixture was extracted withdichloromethane (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4, andconcentrated to give the crude product. The crude product was purified by recrystallizationfrom ethanol. All the products were characterized by comparison of their melting pointswith known compounds and 1H NMR spectra. |
91% | With ZrO2-Al2O3 catalyst In ethanol at 80℃; | |
91% | With Bronsted acidic ionic liquid supported on nano silica In neat (no solvent) at 20℃; for 0.75h; Green chemistry; | General Procedure for the Synthesis of 2,3-Diarylquinoxalines (5a-i) General procedure: In 25 ml round-bottomed flask, a mixture of 1,2-phenylendiamine (1 mmol), benzyl(1 mmol) and BAILnano-SiO2 catalyst (35 mol%) prepared and the reaction mixturewas stirred at room temperature for the appropriate time according to Table 3. The progressof the reaction was monitored by TLC (eluent: ethyl acetate/petroleum ether, 1:7).After completion of the reaction, ethyl acetate (5 mL) was added and the catalyst wasseparated by simple filtration. Residue was dried over anhydrous Na2SO4 and after evaporationof solvent the pure product was obtained by recrystallization from ethanol. |
90% | With niobium pentachloride In acetonitrile at 20℃; for 0.166667h; | |
90% | at 120℃; for 0.666667h; Green chemistry; | |
90% | With Tween 40 In water at 20℃; for 0.333333h; Green chemistry; | |
90% | With sulfonated rice husk ash at 20℃; for 0.25h; Green chemistry; | General procedure for the synthesis of quinoxaline derivatives General procedure: To a mixture of 1,2-diaminobenzene (1 mmol) and 1,2-dicarbonyl compound (1 mmol), RHA-SO3H (15 mg) was added and the mixture was stirred at room temperature for the appropriate time. The progress of the reaction was monitored by TLC (EtOAc: n-hexane 2:8). After completion of the reaction, ethyl acetate (20 mL) was added to the mixture and the solid catalyst was separated. Then the solvent was evaporated and the resulting solid product was recrystallized from ethanol, producing the pure product in high yields. |
89% | With potassium fluoride on basic alumina at 20℃; for 2h; | General procedure for condensation of α-dicarbonyl compound with o-phenylenediamine: General procedure: A mixture of 1,2-diamine (1 mmol) and α-dicarbonyl compound (1 mmol) was intimately mixed with pre-activated KF-alumina (1:4) (0.5 g) (Basic; Grade: Brockmann 1, and activated by heating under vacuum at 150 °C until bubbling ceases and then cooled to room temperature under vacuum) and stirred solid mixture with a magnetic spin bar at room temperature for hours as indicated in refPreviewPlaceHolderTable 4. After the reaction was complete, the solid mixture washed with diethyl ether (3 × 10 mL) and the solid was filtered off. The filtrate was concentrated and passed through a short column of silica gel to afford the quinoxalines. The desired product was pure on TLC and characterized by spectral (1H and 13C NMR) data and compared to those reported. |
89% | With titanium(IV) oxide at 20℃; for 0.216667h; | |
89% | With Polystyrene-Supported AlCl3 In ethanol for 0.416667h; Reflux; | |
88% | With acetic acid In water at 230℃; for 0.166667h; Microwave irradiation; Green chemistry; | |
87% | In water; glycerol at 90℃; for 4h; | General procedure for synthesis of quinoxoline derivative (Table 2, entry 1): General procedure: To a stirred solution of o-phenylenediamine (0.1 g, 0.92 mmol) in H2O (2 mL), glycerol (5 ml) was added, and the reaction mixture was heated to 90 °C followed by addition of benzyl (0.2 g, 0.92 mmol). The reaction mixture was stirred vigorously at 90 °C. The progress of reaction was monitored by TLC. When all the starting material had been consumed, the reaction was quenched with water (10 mL) and extracted with ethyl acetate (2 × 10 mL). The organic phase was separated and dried over anhydrous Na2SO4 and evaporated under reduced pressure to give crude product. The pure product was isolated by silica gel column chromatography using (EtOAc/hexane, 1:9) |
87% | With zirconium triflate In ethanol; water at 20℃; for 0.5h; Green chemistry; | |
87% | With alkylsulfonate functionalized metal organic framework at 45℃; for 0.283333h; Sonication; | |
86.9% | With 1-butyl-3-methylimidazolium Tetrafluoroborate at 20℃; for 0.5h; Neat (no solvent); | |
86% | With silica supported 12-tungstophosphoric acid nanoparticles In ethanol at 20℃; for 1.46667h; | |
84% | With Dowex 50W In water for 2h; Reflux; Green chemistry; | General procedure General procedure: 1,2-diketones (1.0 mmol), o-aromaticdiamines (1.2 mmol), 5 mL water and Dowex 50W (10 mol%) were taken in a 50 mL Erlenmeyerflask with a condenser and it was refluxed in an oilbath with a specific time period with stirring. Thereaction was monitored by TLC time to time. Afterthe complete conversion of the reaction indicated bybrown spot in TLC then the crude product was cooledand diluted with 5 mL ethanol and Dowex 50W wasseparated by filtration. Solution was concentratedand it was kept in the refrigerator for crystallizationto prepare pure crystals of quinoxaline derivatives.1H-NMR, 13C-NMR and FT-IR spectral data of all theknown compounds (3a-n) were checked with thedata of authentic known compounds. |
82% | With aminosulfonic acid In water at 20℃; for 1h; | |
82% | With aminosulfonic acid In dichloromethane at 20℃; for 2h; | |
80% | In methanol for 1h; Heating; | |
71% | at 75℃; for 4h; Schlenk technique; Inert atmosphere; | |
70% | In ethanol at 20℃; for 2h; Green chemistry; | |
70% | With polyvinylimidazole-based Bronsted acidic ionic liquid grafted silica In ethanol at 20℃; for 1h; | 3.3. General procedure for preparation of quinoxaline derivatives General procedure: To a mixture of 1,2-diketone (1 mmol) and 1,2-diamine (1 mmol) in 4 mL of ethanol was added catalyst III (0.006 g, 0.5 mol%) or catalyst IV (0.017 g, 1 mol%). The reaction mixture was stirred at room temperature for the appropriate time. The progress of the reaction was followed by TLC. Upon completion, the product and the catalyst were separated easily from each other by simple ltration. The ltrate was concentrated under reduced pressure and the crude product was puried by silica gel column chromatography with petroleum ether (bp 60 °C) and ethyl acetate (in some cases recrystallization was used). The obtained quinoxalines were identied by their 1H NMR and 13C NMR spectra and comparison of their melting points with those of the authentic samples. |
65% | With acetic acid; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione at 25℃; for 2h; | 2 [Synthesis of Compound (I-1Db)] After mixing 5.0 g (46.2 mmol) of 1,2-phenylenediamine (I-1 Da), 12.5 g (46.2 mmol) of p-anisyl, and 80 mL of acetic acid, 125 mg of 2-iodoxybenzoic acid was added. After stirring the mixture at 25° C. for 2 hours, the precipitated compound (I-Db) was filtered and washed with 50 mL of methanol (yield 65%). |
59% | With cobalt(III) 5,10,15,20-tetraarylporphyrin In ethanol; water for 1h; Reflux; | |
In ethanol for 24h; Reflux; | General procedure for the synthesis of 2,3-Bis(aryl)quinoxaline-6-carboxylic acid and 2,3-Bis(aryl)quinoxaline: General Procedure: A mixture of 1,2-diketone and 3,4-diaminobenzoic acid or 1,2-phenylenediamine (1.1 equiv.) in EtOH was heated to reflux for 24 h. The reaction mixture was cooled to room temperature and poured into 1: 5 concentrated HCl: H2O. The precipitates were collected by vacuum filtration, washed with H2O, and dried under high vacuum overnight. | |
for 1h; | 4.1 General procedure for the synthesis of compound 3 (using 2,3-diphenylquinoxaline 3aa as an example) General procedure: A stirred solution of deoxybenzoin 1a (196 mg, 1.0 mmol), CuO (88 mg, 1.1 mmol), and iodine (279 mg, 1.1 mmol) was heated at 100 °C for 4 h in DMSO (3 mL), after the disappearance of the starting material (TLC), 1,2-diamine 2a (324 mg, 3.0 mmol) was added and stirred for another 1 h. Then the reaction mixture was poured into 50 mL brine and the aqueous layer was extracted with EtOAc (3×50 mL). The extract was washed with Na2S2O3 solution, dried over anhydrous Na2SO4 then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether/EtOAc as the eluent to give the expected products 3aa as the yellow solid (240 mg, 85% yield). | |
In ethyl acetate; N,N-dimethyl-formamide at 20℃; for 1.5h; | ||
134 mg | With acetic acid In water; toluene; acetonitrile at 60℃; for 2h; Inert atmosphere; | |
With iodine In dimethyl sulfoxide at 20℃; for 12h; | 4.2 General procedure for the synthesis of 3-diphenylquinoxaline 3a General procedure: A mixture of 2-hydroxy-1, 2-diphenylethanone (1.0mmol) and iodine (25mol%) in DMSO (2mL) was stirred at 100°C under an air atmosphere. TLC monitored the end of the reaction. Then the mixture was cooled to room temperature, and benzene-1,2-diamine (1.0mmol) was added into the mixture and stirred for several hours. TLC monitored the end of the reaction. Then H2O (100mL) was added and the mixture was filtered and extracted with ethyl acetate. The combined organic layer was washed by chilled water, dried by Mg2SO4 for 10min, filtered, and evaporated in vacuo. The product was purified by flash column chromatography on silica gel by petroleum ether and ethyl acetate (20:1). White solid was obtained as 3a (0.25g). | |
With graphene oxide In neat (no solvent) at 60℃; for 3h; Sealed tube; Green chemistry; | S2.1. General procedure for the preparation of quinoxaline derivatives: General procedure: A mixture of 2-nitro aniline (1 mmol), hydrazine monohydrate (2.2 mmol) and GO (20 mg) was taken in a screw-capped glass tube and stirred the reaction mixture for 3-4 h at 100 °C temperature. After the complete reduction (as monitored by tlc and by the colour change of the reaction mixture from yellow to total black), 1,2-dicarbonyl compound (or α-hydroxy ketone) (1 mmol) was added to the reaction mixture and stirred for few hours at 60 °C (80 °C for α-hydroxy ketone), as mentioned in the Table 2. After completion of the reaction (checked by tlc), the reaction mixture was cooled to room temperature. Water and ethyl acetate were added to the reaction mixture and centrifuge (5000 rpm) the whole reaction mixture to separate the GO (which is now converted to rGO). This process was repeated for three times. The combined organic-aqueous part was then taken in a separating funnel and the organic layer was separated from aqueous layer, and finally dried over anhydrous Na2SO4. Evaporation of the solvent afforded the desired quinoxaline (satisfactorily pure), which was further purified by passing through a short column of silica gel and using the light petroleum ether:ethyl acetate (97:3) as the eluent. All products were characterized by 1H, 13C NMR data and compared with the reported melting points for known solid compounds. | |
With toluene-4-sulfonic acid In dimethyl sulfoxide at 100℃; for 1h; | General procedure for the synthesis of compounds 3 General procedure: A mixture of 1,2-diaryl-2-hydroxyethanone 1 (1.0 mmol) and PTSA (0.5 mmol) in DMSO (2 mL) was heated to 100 °C (TLC monitored). Then the mixture was added in o-diaminobenzene 2 (1 mmol), and stirred for 1 h. Then the mixture was cooled to room temperature, diluted with brine (30 mL), and extracted with dichloromethane twice (2 x 30 mL). The combined organic layers were dried with MgSO4 and the solvent was removed in vacuo to afford a residue. The residue was purified by column chromatography to afford 3. | |
With nickel nanoparticles supported on Co3O4 nanocages In ethanol at 30℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With tris(para-trifluoromethyl)phenyl phosphine In toluene at 160℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium tetrahydridoborate In tetrahydrofuran; methanol at 20℃; for 2h; | |
98% | With sodium tetrahydridoborate; TiO(acac)2 In acetonitrile at 20℃; for 0.05h; | |
98% | With sodium tetrahydridoborate In lithium hydroxide monohydrate for 0.05h; microwave irradiation; |
98% | With sodium tetrahydridoborate In tetrahydrofuran at 20℃; for 0.333333h; ultrasound irradiation; | |
97% | With Zn(2+)*2BH4(1-)*C6H7NO In acetonitrile at 20℃; for 0.133333h; chemoselective reaction; | Reduction of Benzaldehyde to Benzyl alcoholwith [Zn(BH4)2(2-MeOpy)] General procedure: A Typical ProcedureIn a round-bottomed flask (10 mL),equipped with a magnetic stirrer, a solution ofbanzaldehye (0.106 g, l mmol) in CH3CN (3 mL)was prepared. The complex reducing agent (0.1 g,0.5 mmol) was then added and the mixture wasstirred at room temperature. TLC monitored theprogress of the reaction (eluent; Hexane/EtOAc: 9/1). After completion of the reaction within 1 min, asolution of 5% HCl (5 mL) was added to the reactionmixture and stirred for 5 min. The mixture was extracted with CH2Cl2 (3 × 10 mL) and dried overthe anhydrous sodium sulfate. Evaporation of thesolvent and short column chromatography of theresulting crude material over silica gel (0.015-0.040mm) by eluent of (Hexane/EtOAc: 9/1) afforded thepure liquid benzyl alcohol (0.105 g, 98% yield) |
96% | With mesoporous silica; sodium cyanotrihydridoborate for 0.0291667h; Neat (no solvent); Microwave irradiation; regioselective reaction; | |
96% | With poly(1,4-butyl-bis-vinylpyridinium) borohydride In ethanol at 20℃; for 1.33333h; | |
95% | With Zn(BH4)2(bpy) In acetonitrile at 20℃; | |
95% | With sodium tetrahydridoborate In tetrahydrofuran; lithium hydroxide monohydrate for 0.0666667h; Heating; | |
95% | With zinc(II) tetrahydroborate; zirconium tetrachloride In tetrahydrofuran at 20℃; for 0.833333h; | Typical Procedure for the Reduction of α-Diketones and Acyloins with Zn(BH4)2/ZrCl4System in THF General procedure: In a round-bottomed flask (10 mL)equipped with a magnetic stirrer bar, a solution ofbenzil (0.21 g, l mmol) was prepared in THF (3 mL).To this solution, ZrCl4 (0.4 mmol, 0.93 g) andZn(BH4)2 (0.19 g, 2mmol) was added. The resultingmixture was stirred at room temperature for 40 min.The reaction was monitored by TLC (eluent:CCl4/Et2O:5/2). After completion of the reaction, distilledwater (6 mL) was added to the reaction mixtureand stirred for 5 min. The mixture was extractedwith CH2Cl2 (3×10 mL) and dried over anhydrous Na2SO4. Evaporation of the solvent afforded crystalsof 1,2-diphenyl ethane-1,2-diol (0.19 g, 92% yield). |
94% | With C8H18B2N4O2Zn In acetonitrile for 1h; Reflux; | |
93% | With sodium tetrahydridoborate; sodium hydrogen sulphate In acetonitrile at 20℃; for 0.116667h; | |
93% | With sodium tetrahydridoborate; pyrographite In tetrahydrofuran; lithium hydroxide monohydrate at 20℃; for 0.1h; | |
93% | With 2BH4(1-)*Zn(2+)*Cl2Na2 In acetonitrile at 20℃; for 0.25h; | 2.4. Typical Procedure for the Reduction of Ketones withZn(BH4)2/2NaCl System in CH3CN General procedure: In a round-bottomed flask (10 mL), equipped with a magneticstirrer bar, a solution of acetophenone (0.121 g, l mmol) was prepared in CH3CN(3 mL). To this solution, Zn(BH4)2/2NaCl (0.210 g,1 mmol) was added. The resulting mixture was stirred at room temperature for 60 min. The reaction was monitored by TLC(eluent; Hexane/EtOAc: 10/1). After completion of the reaction, distilled water (5 mL) was added to the reaction mixture and stirred for 5 min. The mixture was extracted with CH2Cl2 (3 ×8 mL) and dried over anhydrous Na2SO4. Evaporation of the solvent followed column chromatography of the resulting crude material over silica gel (eluent; Hexane/EtOAc: 10/1) afforded crystals of 1-phenylethanol (0.l1 g, 93 % yield,Table 2, entry 11). |
92% | With sodium tetrahydridoborate; diammonium oxalate In acetonitrile for 1h; Reflux; | |
92% | With zinc(II) tetrahydroborate In tetrahydrofuran; lithium hydroxide monohydrate at 20℃; for 0.583333h; | |
92% | With aluminum(III) oxide; zinc(II) tetrahydroborate In tetrahydrofuran at 20℃; for 0.33h; chemoselective reaction; | A typical procedure for reduction of α-diketones and acyloins with the Zn(BH4)2/Al2O3 systemin THF General procedure: In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a solution of benzil(0.21 g, 1 mmol) in THF (3 mL was prepared. To this solution, Zn(BH4)2 (0.190 g, 2 mmol)and then neutral Al2O3 (0.101 g, 1 mmol) were added. The resulting mixture was stirred atroom temperature for 20 min. The progress of the reaction was monitored by TLC (eluent,CCl4/Et2O: 5/2). After completion of the reaction, distilled water (1 mL) was added to thereaction mixture and stirring was continued for an additional 5 min. The mixture was extractedwith CH2Cl2 (3×10 mL) and dried over anhydrous sodium sulfate. Evaporation of thesolvent and short column chromatography of the resulting crude material over abovementioned silica gel afforded pure crystals of 1,2-diphenylethane-1,2-diol (0.20 g, 95 % yield,Table V, entry 1). |
92% | With sodium tetrahydridoborate In tetrahydrofuran at 20℃; for 0.25h; | |
90% | With [Zn(tetrahydroborato)2(acridine)] In acetonitrile for 1.33333h; Reflux; | Reduction of Acetophenone to 1-phenylethanolwith [Zn(BH4)2(acr)], A Typical Procedure General procedure: In a round-bottomed flask (10 mL),equipped with a magnetic stirrer, a solution ofacetophenone (0.120 g, 1mmol) in CH3CN (3 mL)was prepared. The complex reducing agent (0.274g, 1mmol) was then added as a solid and the mixturewas stirred at reflux conditions. TLC monitored theprogress of the reaction (eluent; CCl4/Et2O : 5/2). After completion of the reaction in 90 min, a solutionof 5% HCl (5 mL) was added to the reaction mixtureand stirred for 10 min. The mixture was extractedwith CH2Cl2(3 × 10 mL) and dried over theanhydrous sodium sulfate. Evaporation of thesolvent and short column chromatography of theresulting crude material over silica gel by eluent ofCCl4/Et2O : 5/2 afforded the pure liquid benzylalcohol (0.113 g, 93% yield). |
88% | In N,N-dimethyl-formamide at 110℃; for 10h; | |
85% | With Poly(n-butyl-4-vinylpyridinium)borohydride In ethanol at 20℃; for 3.9h; | General procedure for the reduction of carbonylcompounds with P(BVP)BH4 General procedure: To a solution of the substrate (1 mmol) in ethanol as asolvent (5 mL) in a round-bottomed flask (25 mL) equippedwith a magnetic stirrer, P(BVP)BH4 (100 mg) was addedand stirred at room temperature. The progress of thereaction was monitored by TLC. On completion of thereaction, the mixture was filtered and the used reagent waswashed successively with HCl (1.0 M, 2 10 mL) andethanol (2 5 mL). The combined filtrates were evaporatedand the pure product was obtained in moderate to excellent yields. In a few cases in which the reaction wasnot complete, the crude product was purified on silica gelwith an appropriate eluent (Scheme 1). |
76% | With Ca(BH2S3)2 In tetrahydrofuran for 7.5h; Heating; | |
75% | With sodium tetrahydridoborate In ethanol at 25℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | at 80℃; for 1h; solid-state reaction; | |
100% | With zirconium(IV) chloride In methanol at 20℃; for 0.5h; | |
99% | With aluminum oxide at 20℃; for 0.166667h; neat (no solvent); |
99% | With Cs(cetyltrimethylammonium)<SUB>2</SUB>PW<SUB>12</SUB>O<SUB>40</SUB> In neat (no solvent) at 80℃; for 1.5h; Green chemistry; | 2.3. General method for the preparation of quinoxalinederivatives A mixture of 1,2-dicarbonyl (1 mmol) and 1,2-diamine(1 mmol) derivatives in the presence of an appropriateamount of the Cs(CTA)2PW12O40 catalyst was stirred at agiven temperature. The progress of the reaction wasmonitored by thin layer chromatography (TLC). Aftercompletion of the reaction, 5 mL of hot ethanol was addedto the reaction mixture and the solid catalyst was filtered.The pure products were obtained after crystallizationand analyzed without any further purification. All ofthe obtained quinoxalines are known compounds andidentified by 1H NMR and melting points compared withthe literature values. The melting points, spectral (1H NMR)and elemental analysis data for the products are givenbelow. |
98% | With potassium hydrogensulfate In ethanol at 20℃; for 0.2h; | |
98% | With silica-supported stannous chloride In methanol at 20℃; for 0.416667h; | |
98% | With sulfonated rice husk ash at 20℃; for 0.166667h; Green chemistry; | General procedure for the synthesis of quinoxaline derivatives General procedure: To a mixture of 1,2-diaminobenzene (1 mmol) and 1,2-dicarbonyl compound (1 mmol), RHA-SO3H (15 mg) was added and the mixture was stirred at room temperature for the appropriate time. The progress of the reaction was monitored by TLC (EtOAc: n-hexane 2:8). After completion of the reaction, ethyl acetate (20 mL) was added to the mixture and the solid catalyst was separated. Then the solvent was evaporated and the resulting solid product was recrystallized from ethanol, producing the pure product in high yields. |
97% | In acetic acid at 20℃; for 0.333333h; | |
97% | With ziconium(IV) oxychloride octahydrate In ethanol at 25℃; for 0.333333h; | |
96% | In acetonitrile at 25℃; for 0.0833333h; | |
96% | With 1-butylimidazolium tetrafluoroborate at 20℃; for 0.666667h; | |
96% | With aluminum oxide at 80℃; for 1.25h; Neat (no solvent); | |
96% | With polyaniline/SiO2 In ethanol at 20℃; for 0.216667h; | |
96% | With zirconium oxide salicylaldehyde-(3-aminopropyl)trimethoxysilane imine complex modified SBA-15 In water for 3h; Reflux; | |
96% | With mesoporous silica SBA-15 functionalized with Cu(II)-DiAmSar complex In neat (no solvent) at 100℃; for 0.333333h; | 2.3. General procedure for the synthesis of pyrazine-basedheterocycles under solvent-free conditions General procedure: A round-bottomed flask equipped with a magnet and condenserwas charged with the desired 1,2-diamine (1.0 mmol),1,2-diketone (1.0 mmol), and catalyst (Cu(II)DiAmSar/SBA-15,0.005 g). The resulting mixture was heated at 100 °C for theappropriate time. The course of the reaction was monitoredusing TLC on silica gel. Finally, the reaction mixture was cooled,and the crude mixture was purified by column chromatographyor crystallization to get the desired product. Spectral and physicaldata for all heterocycles were compared with referencesamples and were in accord with previously reported data. |
95% | With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate In water at 20℃; for 0.416667h; | |
95% | With ZnO-β-zeolite In ethanol at 20℃; for 0.2h; | |
95% | With 1-(propyl-3-sulfonate) 3-methylimidazol(3H)-1-ium phosphotungstate In water at 20℃; for 0.233333h; | |
95% | In neat (no solvent) at 20℃; for 0.416667h; Green chemistry; | General procedure for the synthesis of quinoxalines under solventless conditions General procedure: A mixture of 1,2-phenylenediamine derivative (1 mmol), 1,2-diketones (1 mmol) and nano SbCl5.SiO2 (62%w/w ) (0.15 g) was stirred at room temperature under solventless condition. The reaction was monitored by TLC (n-hexane:ethyl acetate, 7:3). After completion of the reaction, the mixture was washed with chloroform (2×5 mL) and filtered to recover the catalyst. The solvent was evaporated and the crude product was recrystallized from ethanol (5 mL) to afford pure quinoxaline derivatives. |
95% | With H3PMo12O40 nanoparticles immobilized on imidazole functionalized core-shell Fe3O4(at)SiO2 nanoparticle In ethanol at 20℃; for 0.166667h; Green chemistry; | 5.1 2.2.4. General procedure for the preparation of quinoxaline derivatives General procedure: To a stirred solution of amine (1 mmol) and carbonyl compounds (1 mmol) in EtOH (5 mL) were added Fe3O4SiO2-imid-PMAn (0.03 g, 0.5 mol%). The progress of the reaction was followed by thin-layer chromatography (TLC). After completion of the reaction, ethyl acetate was added to the solidified mixture and the insoluble catalyst was separated by magnetic field. The filtrate was dried and organic medium was removed with a rotary evaporator under reduced pressure. The crude products were crystallized from ethanol to afford pure products for analytical measurements. |
94% | With vitamin B1 In methanol at 25℃; for 0.416667h; Sonication; | |
94% | With C20H24Cl2N2O2Zr In ethanol at 20℃; for 0.833333h; Green chemistry; | |
94% | With nitrilo-tris(methylenephosphonic acid) In ethanol; water at 20℃; for 0.416667h; Green chemistry; | General Experimental Procedure for the Synthesis of Quinoxaline Derivatives General procedure: A mixture of 1,2-diamines (1 mmol) and 1,2-dicarbonyls (1 mmol) in ethanol (3 mL)was poured to the solution of NTMPA (5 mol%, 15 mg) in distilled water (3 mL) atroom temperature. The reaction was monitored by thin-layer chromatography (TLC). Aftercompletion of the reaction, water (10 mL) was added, and the mixture was extracted withdichloromethane (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4, andconcentrated to give the crude product. The crude product was purified by recrystallizationfrom ethanol. All the products were characterized by comparison of their melting pointswith known compounds and 1H NMR spectra. |
93% | With zirconium tetrakis(dodecyl sulfate) In water at 20℃; for 0.583333h; | |
93% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With ZrOL2(at)SMNP In ethanol at 25℃; for 0.0333333h; Stage #2: 4-methyl-1,2-diaminobenzene In ethanol at 60℃; for 0.333333h; | General procedure for the synthesis of quinoxalines and pyrido pyrazines General procedure: A mixture of the required 1,2-dicarbonyl (1 mmol) and ZrOL2&SMNP (0.004 g) in ethanol (0.5 ml) was stirred at 25°C for 2 min. Then, the required 1,2-diamine (1.5 mmol) was added to the mixture, which was stirred at 60 °C for the appropriate reaction time. The progress of the reaction was monitored by TLC or GC. After completion of the reaction, the precipitate was dissolved by adding ethanol, and ZrOL2&SMNP was separated by decantation of the reaction mixture in the presence of an external magnet. Most of the product was precipitated purely by concentrating and cooling the ethanolic solution. There maining product was isolated from an excess of 1,2-diamine by plate chromatography eluted with n-hexane-EtOAc (10/2). Structural assignments of the products were based on their 1H and 13C NMR spectra. |
92% | With titanium(IV) oxide In 1,2-dichloro-ethane at 25℃; for 1h; | |
92% | With nano-BF3*SiO2 at 20℃; for 0.133333h; Neat (no solvent); | |
92.3% | With 1-butyl-3-methylimidazolium Tetrafluoroborate at 20℃; for 0.25h; Neat (no solvent); | |
92% | at 120℃; for 0.666667h; Green chemistry; | |
92% | With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 80℃; for 0.133333h; | |
92% | With silica-supported bismuth(III) chloride In methanol at 20℃; for 0.5h; | 4.1 2.3 General procedure for the acid-catalyzed benzo[N,N]-heterocyclic condensation General procedure: A mixture of arene-1,2-diamine (1.2mmol), 1,2-dicarbonyl (1mmol), and 0.20g of BiCl3/SiO2 (5mol %) was taken in methanol (5mL) and stirred at room temperature for the appropriate reaction time (Scheme 1). After completion of the reaction (monitored by TLC using ethyl acetate/hexane (2:8 v/v) or GC), dichloromethane was added to the reaction mixture and the catalyst was recovered by filtration. The organic medium was removed with rotary evaporator under reduced pressure. The crude products were purified by column chromatography using ethyl acetate/hexane (2:8 v/v) [dichloromethane/ethanol (9:1 v/v) for products 1h-1m] to afford pure products for analytical measurements. The products were identified by comparison of their NMR and mass spectra with authentic samples. |
92% | With Bronsted acidic ionic liquid supported on nano silica In neat (no solvent) at 20℃; for 0.75h; Green chemistry; | General Procedure for the Synthesis of 2,3-Diarylquinoxalines (5a-i) General procedure: In 25 ml round-bottomed flask, a mixture of 1,2-phenylendiamine (1 mmol), benzyl(1 mmol) and BAILnano-SiO2 catalyst (35 mol%) prepared and the reaction mixturewas stirred at room temperature for the appropriate time according to Table 3. The progressof the reaction was monitored by TLC (eluent: ethyl acetate/petroleum ether, 1:7).After completion of the reaction, ethyl acetate (5 mL) was added and the catalyst wasseparated by simple filtration. Residue was dried over anhydrous Na2SO4 and after evaporationof solvent the pure product was obtained by recrystallization from ethanol. |
92% | With C15H30N2O6S2(2+)*2HO4S(1-) In ethanol at 80℃; for 0.5h; | General procedure: A 25-mL round-bottom flask was charged with the benzil 1 (1 mmol), OPD 2(1 mmol), catalyst IL [BBSA-DBN][HSO4] (3 mol.% with respect to 1,2-diketones)and ethanol (5 mL). The whole reaction mixture was heated in an oil bathat 80 °C for the stipulated period of time (Table 3) till the completion of the reaction(monitored by TLC). After completion of reaction, the reaction mixture wascooled to room temperature and diluted with water (10 mL) and again stirred for5 min, then the reaction mixture was filtered to recover the catalyst, and the filtrate was concentrated under vacuum. The crude product was purified by recrystallizationwith 96% ethanol to give the pure product 3a. Authenticity of some synthesizedproducts 3a-s has been confirmed by using FTIR, 1H NMR, 13C NMR and Mass spectroscopic techniques. |
92% | With 2-methylenesuccinic acid In water at 20℃; for 1h; Schlenk technique; Green chemistry; | |
91% | With manganese(ll) chloride In ethanol at 20℃; for 0.166667h; | |
91% | With titanium(IV) oxide at 20℃; for 0.15h; | |
91% | With Thiamine hydrochloride In ethanol at 20℃; for 0.25h; | |
90% | In dimethyl sulfoxide at 20℃; for 1h; | |
90% | In water; glycerol at 90℃; for 6h; | General procedure for synthesis of quinoxoline derivative (Table 2, entry 1): General procedure: To a stirred solution of o-phenylenediamine (0.1 g, 0.92 mmol) in H2O (2 mL), glycerol (5 ml) was added, and the reaction mixture was heated to 90 °C followed by addition of benzyl (0.2 g, 0.92 mmol). The reaction mixture was stirred vigorously at 90 °C. The progress of reaction was monitored by TLC. When all the starting material had been consumed, the reaction was quenched with water (10 mL) and extracted with ethyl acetate (2 × 10 mL). The organic phase was separated and dried over anhydrous Na2SO4 and evaporated under reduced pressure to give crude product. The pure product was isolated by silica gel column chromatography using (EtOAc/hexane, 1:9) |
90% | With iodine | |
89% | With niobium pentachloride In acetonitrile at 20℃; for 0.333333h; | |
88% | With Polystyrene-Supported AlCl3 In ethanol for 0.5h; Reflux; | |
84% | With aminosulfonic acid In water at 20℃; for 3h; | |
84% | With aminosulfonic acid In dichloromethane at 20℃; for 6h; | |
82% | With silica supported 12-tungstophosphoric acid nanoparticles In ethanol at 20℃; for 0.466667h; | |
62% | With cobalt(III) 5,10,15,20-tetraarylporphyrin In ethanol; water for 1h; Reflux; | |
With iodine In dimethyl sulfoxide at 20℃; for 12h; | 4.2 General procedure for the synthesis of 3-diphenylquinoxaline 3a General procedure: A mixture of 2-hydroxy-1, 2-diphenylethanone (1.0mmol) and iodine (25mol%) in DMSO (2mL) was stirred at 100°C under an air atmosphere. TLC monitored the end of the reaction. Then the mixture was cooled to room temperature, and benzene-1,2-diamine (1.0mmol) was added into the mixture and stirred for several hours. TLC monitored the end of the reaction. Then H2O (100mL) was added and the mixture was filtered and extracted with ethyl acetate. The combined organic layer was washed by chilled water, dried by Mg2SO4 for 10min, filtered, and evaporated in vacuo. The product was purified by flash column chromatography on silica gel by petroleum ether and ethyl acetate (20:1). White solid was obtained as 3a (0.25g). | |
With graphene oxide In neat (no solvent) at 60℃; for 3h; Sealed tube; Green chemistry; | S2.1. General procedure for the preparation of quinoxaline derivatives: General procedure: A mixture of 2-nitro aniline (1 mmol), hydrazine monohydrate (2.2 mmol) and GO (20 mg) was taken in a screw-capped glass tube and stirred the reaction mixture for 3-4 h at 100 °C temperature. After the complete reduction (as monitored by tlc and by the colour change of the reaction mixture from yellow to total black), 1,2-dicarbonyl compound (or α-hydroxy ketone) (1 mmol) was added to the reaction mixture and stirred for few hours at 60 °C (80 °C for α-hydroxy ketone), as mentioned in the Table 2. After completion of the reaction (checked by tlc), the reaction mixture was cooled to room temperature. Water and ethyl acetate were added to the reaction mixture and centrifuge (5000 rpm) the whole reaction mixture to separate the GO (which is now converted to rGO). This process was repeated for three times. The combined organic-aqueous part was then taken in a separating funnel and the organic layer was separated from aqueous layer, and finally dried over anhydrous Na2SO4. Evaporation of the solvent afforded the desired quinoxaline (satisfactorily pure), which was further purified by passing through a short column of silica gel and using the light petroleum ether:ethyl acetate (97:3) as the eluent. All products were characterized by 1H, 13C NMR data and compared with the reported melting points for known solid compounds. | |
With toluene-4-sulfonic acid In dimethyl sulfoxide at 100℃; for 1h; | General procedure for the synthesis of compounds 3 General procedure: A mixture of 1,2-diaryl-2-hydroxyethanone 1 (1.0 mmol) and PTSA (0.5 mmol) in DMSO (2 mL) was heated to 100 °C (TLC monitored). Then the mixture was added in o-diaminobenzene 2 (1 mmol), and stirred for 1 h. Then the mixture was cooled to room temperature, diluted with brine (30 mL), and extracted with dichloromethane twice (2 x 30 mL). The combined organic layers were dried with MgSO4 and the solvent was removed in vacuo to afford a residue. The residue was purified by column chromatography to afford 3. | |
With nickel nanoparticles supported on Co3O4 nanocages In ethanol at 30℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With ammonium acetate In ethanol at 40℃; for 0.583333h; Sonication; Green chemistry; | 2.4. General procedure for the synthesis of 2,4,5-trisubstituted imidazoles ultrasonic irradiation General procedure: A 25 mL Erlenmeyer flask was charged with benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (0.4 g, 5 mmol), SA-MNPs (0.1 g) and ethanol (10 mL). The reaction flask was located in the ultrasonic bath, where the surface of reactants is slightly lower than the level of the water, and irradiated under 20, 40, 60, 80 and 100% of the power of the ultrasonic bath and the temperature inside the reactor at 40 °C for the period of time (The reaction was monitored by TLC) separately as indicated in Table 4. After the reaction was completed, the catalyst was separated by an external magnet and reused as such for the next experiment. The reaction mixture was concentrated on a rotary evaporator under reduced pressure and the solid product obtained was dissolved in acetone and filtered. The solid product obtained was washed with water and recrystallized from acetone-water 9:1 (v/v) to offer pure product 3a in 98% yield. All products were known and characterized by comparison of their physical and spectra data with those already reported [31]. |
93% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; | |
92% | With ammonium acetate In acetic acid at 120℃; |
91% | With ammonium acetate In neat (no solvent) at 110℃; for 0.166667h; Microwave irradiation; Green chemistry; | 2.2.1. General procedure for the synthesis of 2,4,5-trisubstituted imidazole derivatives (3a-c) General procedure: The mixture of 4,4′-dimethoxybenzil (1 mmol), aromatic aldehyde (1 mmol), and ammonium acetate (2 mmol) were transferred to a clean and dry mortar, triturated to form a uniform mixture. The resulting mixture was then transferred to a 10 mL microwave vessel and it was heated at 110 °C using microwave irradiation (300 W) for 10 min. The reaction was monitored by TLC (hexane: ethyl acetate 7:3 v/v) and the products were allowed to cool to room temperature. The resulting residue was directly purified by column chromatography using hexane: ethyl acetate 7:3 v/v as eluent. |
90% | With ammonium acetate In ethanol for 3.5h; Reflux; Green chemistry; | |
72% | With ammonium acetate In ethanol at 78℃; Green chemistry; | General procedure General procedure: A mixture of 1,2-diketone (0.5 mmol), aldehyde (0.5 mmol),ammonium acetate (1.5 mmol) and Fe3O4g-C3N4 (20 mg)in ethanol (1 mL) was heated at 78 °C with stirring for120-200 min. After the completion of the reaction, ethanolwas added and the Fe3O4g-C3N4 was separated magneticallyusing a bar magnet. The reaction mixture was allowedto cool to room temperature to recrystallize from ethanolto get the pure final product. All compounds were knownand characterized on the basis of their melting point and bycomparison with those reported in the literature. |
68% | With ammonium acetate at 20℃; | |
53% | With ammonium acetate In acetic acid for 12h; Heating; | |
With ammonium acetate; acetic acid Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With ruthenium trichloride; bromamine T In water; acetonitrile at 80℃; for 0.133333h; | |
96% | With N-methylpyrrolidine-2-one hydrotribromide; dihydrogen peroxide In acetonitrile for 1h; Heating; | |
95% | With magnesium sulfate In acetonitrile for 5.5h; Heating; |
92% | With oxygen In toluene at 90℃; for 3.5h; | |
91% | With pyridine; antimony(III) bromide; phenyltrimethylammonium tribromide In methanol at 20℃; for 14h; | |
91% | With ammonium chlorochromate supported on montmorillonite K10 In dichloromethane at 22 - 27℃; for 1.16667h; ultrasound; | |
91% | With urea hydrogen peroxide adduct; lanthanum(lll) triflate at 70℃; for 0.583333h; Ionic liquid; Green chemistry; | General procedure for the oxidation of 1,2-diols (1a-i) to 1,2-diketones (2a-i) General procedure: A mixture of 1,2-diol (1) (1.0 mmol), UHP (2.0 mmol), 10 mol% (CF3SO3)3La and [bmim]BF4(5 mmol) was placed in a 50 mL RB flask fitted with a calcium chloride guard tube. The reactionmixture was stirred magnetically in an oil-bath maintained at 70°C for an appropriate time asmentioned in Table 2. The progress of the reaction was monitored by TLC using petroleumether:ethyl acetate (70:30). After completion of the reaction, the reaction mixture was cooled toroom temperature and washed with diethyl ether (3×10 mL). The combined ethereal layer waswashed with water (2×10 mL) and dried over anhyd. Na2SO4. The ethereal extract wasconcentrated on a rotary evaporator to give corresponding 1,2-diketone. |
87% | With N-Bromosuccinimide; 1-butyl-3-methylimidazolium Tetrafluoroborate at 70℃; for 2h; | |
85.5% | With [Bmim][Br3]; sodium acetate at 60℃; for 1h; | |
84% | With 1-butyl-3-methylimidazolium hydrogen sulfate; sodium bromate In water at 60℃; for 0.75h; Green chemistry; | General procedure for the oxidation of 1,2-diols, a-hydroxyketones and alcohols to 1,2-diketones and aldehydes/ketones General procedure: In a typical experiment, a mixture of 1,2-diols/a-hydroxyketones/alcohols (1 mmol), sodium bromate (3 mmol),and bmim[HSO4]:H2O 3:1 (v/v) along with a stir bar was placed in a RB flask fitted with a condenser. The reaction mixture was stirred magnetically in an oil-bath maintained at 60 C for an appropriate time as mentioned in Tables 3,4, and 5, respectively. After completion of the reaction, as monitored by TLC using petroleum ether:ethyl acetate(80:20, v/v) as eluent, the reaction mixture was cooled to room temperature and worked up as mentioned above. The product obtained was identified by m.p (wherever applicable), IR and NMR spectra. |
83% | With pyridine; N-Bromosuccinimide In tetrachloromethane for 1.5h; Heating; | |
11% | With oxygen; sodium t-butanolate at -20℃; | |
With N-Bromosuccinimide | ||
Multi-step reaction with 2 steps 1: sodium bromate; 1-butyl-3-methylimidazolium hydrogen sulfate / water / 1.5 h / 20 °C / Green chemistry 2: sodium bromate; 1-butyl-3-methylimidazolium hydrogen sulfate / water / 0.5 h / 60 °C / Green chemistry | ||
With hydrogen bromide In dimethyl sulfoxide at 90℃; for 3h; | 2.b (b) The crude product IIb is dried and dissolved in 400 ml of DMSO.180 ml of 48% hydrobromic acid solution was added under stirring.After stirring at 90 ° C for three hours, the reaction was monitored by TLC until the reaction was completed.The reaction solution was poured into 6 volumes of purified water while stirring. After stirring for 3-5 minutes, it was allowed to stand overnight, and the precipitate was filtered, and the precipitate was washed with 300 ml of water.Obtaining the crude compound IIIb; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With zirconium(IV) chloride In methanol at 20℃; for 2h; | |
97% | With silica-supported stannous chloride In methanol at 20℃; for 1h; | |
95% | With silica-supported bismuth(III) chloride In methanol at 20℃; for 1.5h; | 4.1 2.3 General procedure for the acid-catalyzed benzo[N,N]-heterocyclic condensation General procedure: A mixture of arene-1,2-diamine (1.2mmol), 1,2-dicarbonyl (1mmol), and 0.20g of BiCl3/SiO2 (5mol %) was taken in methanol (5mL) and stirred at room temperature for the appropriate reaction time (Scheme 1). After completion of the reaction (monitored by TLC using ethyl acetate/hexane (2:8 v/v) or GC), dichloromethane was added to the reaction mixture and the catalyst was recovered by filtration. The organic medium was removed with rotary evaporator under reduced pressure. The crude products were purified by column chromatography using ethyl acetate/hexane (2:8 v/v) [dichloromethane/ethanol (9:1 v/v) for products 1h-1m] to afford pure products for analytical measurements. The products were identified by comparison of their NMR and mass spectra with authentic samples. |
94% | With 1-(propyl-3-sulfonate) 3-methylimidazol(3H)-1-ium phosphotungstate In water at 20℃; for 0.183333h; | |
93% | With H3PMo12O40 nanoparticles immobilized on imidazole functionalized core-shell Fe3O4(at)SiO2 nanoparticle In ethanol at 20℃; for 0.25h; Green chemistry; | 5.1 2.2.4. General procedure for the preparation of quinoxaline derivatives General procedure: To a stirred solution of amine (1 mmol) and carbonyl compounds (1 mmol) in EtOH (5 mL) were added Fe3O4SiO2-imid-PMAn (0.03 g, 0.5 mol%). The progress of the reaction was followed by thin-layer chromatography (TLC). After completion of the reaction, ethyl acetate was added to the solidified mixture and the insoluble catalyst was separated by magnetic field. The filtrate was dried and organic medium was removed with a rotary evaporator under reduced pressure. The crude products were crystallized from ethanol to afford pure products for analytical measurements. |
92% | In acetonitrile at 25℃; for 0.166667h; | |
91% | In water; glycerol at 90℃; for 6h; | General procedure for synthesis of quinoxoline derivative (Table 2, entry 1): General procedure: To a stirred solution of o-phenylenediamine (0.1 g, 0.92 mmol) in H2O (2 mL), glycerol (5 ml) was added, and the reaction mixture was heated to 90 °C followed by addition of benzyl (0.2 g, 0.92 mmol). The reaction mixture was stirred vigorously at 90 °C. The progress of reaction was monitored by TLC. When all the starting material had been consumed, the reaction was quenched with water (10 mL) and extracted with ethyl acetate (2 × 10 mL). The organic phase was separated and dried over anhydrous Na2SO4 and evaporated under reduced pressure to give crude product. The pure product was isolated by silica gel column chromatography using (EtOAc/hexane, 1:9) |
91% | With vitamin B1 In methanol at 25℃; for 1h; Sonication; | |
90% | With polyaniline/SiO2 In ethanol at 20℃; for 0.45h; | |
89% | With 2-methylenesuccinic acid In water at 20℃; for 1h; Schlenk technique; Green chemistry; | |
88% | With niobium pentachloride In acetonitrile at 20℃; for 0.416667h; | |
87% | With Polystyrene-Supported AlCl3 In ethanol for 0.583333h; Reflux; | |
83% | With nitrilo-tris(methylenephosphonic acid) In ethanol; water at 20℃; for 0.416667h; Green chemistry; | General Experimental Procedure for the Synthesis of Quinoxaline Derivatives General procedure: A mixture of 1,2-diamines (1 mmol) and 1,2-dicarbonyls (1 mmol) in ethanol (3 mL)was poured to the solution of NTMPA (5 mol%, 15 mg) in distilled water (3 mL) atroom temperature. The reaction was monitored by thin-layer chromatography (TLC). Aftercompletion of the reaction, water (10 mL) was added, and the mixture was extracted withdichloromethane (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4, andconcentrated to give the crude product. The crude product was purified by recrystallizationfrom ethanol. All the products were characterized by comparison of their melting pointswith known compounds and 1H NMR spectra. |
79% | With aminosulfonic acid In dichloromethane at 20℃; for 6h; | |
75% | With aminosulfonic acid In water at 20℃; for 3h; | |
With iodine In dimethyl sulfoxide at 20℃; for 12h; | 4.2 General procedure for the synthesis of 3-diphenylquinoxaline 3a General procedure: A mixture of 2-hydroxy-1, 2-diphenylethanone (1.0mmol) and iodine (25mol%) in DMSO (2mL) was stirred at 100°C under an air atmosphere. TLC monitored the end of the reaction. Then the mixture was cooled to room temperature, and benzene-1,2-diamine (1.0mmol) was added into the mixture and stirred for several hours. TLC monitored the end of the reaction. Then H2O (100mL) was added and the mixture was filtered and extracted with ethyl acetate. The combined organic layer was washed by chilled water, dried by Mg2SO4 for 10min, filtered, and evaporated in vacuo. The product was purified by flash column chromatography on silica gel by petroleum ether and ethyl acetate (20:1). White solid was obtained as 3a (0.25g). | |
With toluene-4-sulfonic acid In dimethyl sulfoxide at 100℃; for 1h; | General procedure for the synthesis of compounds 3 General procedure: A mixture of 1,2-diaryl-2-hydroxyethanone 1 (1.0 mmol) and PTSA (0.5 mmol) in DMSO (2 mL) was heated to 100 °C (TLC monitored). Then the mixture was added in o-diaminobenzene 2 (1 mmol), and stirred for 1 h. Then the mixture was cooled to room temperature, diluted with brine (30 mL), and extracted with dichloromethane twice (2 x 30 mL). The combined organic layers were dried with MgSO4 and the solvent was removed in vacuo to afford a residue. The residue was purified by column chromatography to afford 3. | |
With nickel nanoparticles supported on Co3O4 nanocages In ethanol at 30℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With titanium(IV) oxide In 1,2-dichloro-ethane at 25℃; for 1.5h; | |
94% | With zirconium triflate In ethanol; water at 20℃; for 0.333333h; Green chemistry; | |
93% | With H3PMo12O40 nanoparticles immobilized on imidazole functionalized core-shell Fe3O4(at)SiO2 nanoparticle In ethanol at 20℃; for 0.333333h; Green chemistry; | 5.1 2.2.4. General procedure for the preparation of quinoxaline derivatives General procedure: To a stirred solution of amine (1 mmol) and carbonyl compounds (1 mmol) in EtOH (5 mL) were added Fe3O4SiO2-imid-PMAn (0.03 g, 0.5 mol%). The progress of the reaction was followed by thin-layer chromatography (TLC). After completion of the reaction, ethyl acetate was added to the solidified mixture and the insoluble catalyst was separated by magnetic field. The filtrate was dried and organic medium was removed with a rotary evaporator under reduced pressure. The crude products were crystallized from ethanol to afford pure products for analytical measurements. |
90% | With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide In neat (no solvent) at 80℃; for 0.333333h; | |
89% | With potassium fluoride on basic alumina at 20℃; for 2h; | General procedure for condensation of α-dicarbonyl compound with o-phenylenediamine: General procedure: A mixture of 1,2-diamine (1 mmol) and α-dicarbonyl compound (1 mmol) was intimately mixed with pre-activated KF-alumina (1:4) (0.5 g) (Basic; Grade: Brockmann 1, and activated by heating under vacuum at 150 °C until bubbling ceases and then cooled to room temperature under vacuum) and stirred solid mixture with a magnetic spin bar at room temperature for hours as indicated in refPreviewPlaceHolderTable 4. After the reaction was complete, the solid mixture washed with diethyl ether (3 × 10 mL) and the solid was filtered off. The filtrate was concentrated and passed through a short column of silica gel to afford the quinoxalines. The desired product was pure on TLC and characterized by spectral (1H and 13C NMR) data and compared to those reported. |
88% | In dimethyl sulfoxide at 20℃; for 1.25h; | |
88% | With iodine | |
81% | With silica-supported bismuth(III) chloride In methanol at 20℃; for 1.5h; | 4.3 2.3 General procedure for the acid-catalyzed benzo[N,N]-heterocyclic condensation General procedure: A mixture of arene-1,2-diamine (1.2mmol), 1,2-dicarbonyl (1mmol), and 0.20g of BiCl3/SiO2 (5mol %) was taken in methanol (5mL) and stirred at room temperature for the appropriate reaction time (Scheme 1). After completion of the reaction (monitored by TLC using ethyl acetate/hexane (2:8 v/v) or GC), dichloromethane was added to the reaction mixture and the catalyst was recovered by filtration. The organic medium was removed with rotary evaporator under reduced pressure. The crude products were purified by column chromatography using ethyl acetate/hexane (2:8 v/v) [dichloromethane/ethanol (9:1 v/v) for products 1h-1m] to afford pure products for analytical measurements. The products were identified by comparison of their NMR and mass spectra with authentic samples. |
81% | With alkylsulfonate functionalized metal organic framework at 45℃; for 0.4h; Sonication; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium hydroxide; In ethanol; at 70℃; for 3h;Inert atmosphere; | (2) Intermediate product 2 (3.69 g, 10 mmol), 4,4'-dimethoxyphenol ester (Compound 3) (2.7 g, 10 mmol) and potassium hydroxide (0.168 g, 3 mmol) were added to the reaction flask, pumped three times, and solvent ethanol (30mL) was injected under nitrogen protection. The resulting mixture was refluxed at 70 C for three hours. After completion of the reaction, the reaction flask was cooled in an ice bath and precipitated to obtain the product. The product was washed with cold ethanol and dried to give red powder product 4 (compound 4). Yield 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In acetic acid at 20℃; for 0.333333h; | |
96% | With zirconium(IV) chloride In methanol at 50℃; for 4h; | |
96% | With polyaniline/SiO2 In ethanol at 20℃; for 0.3h; |
96% | With 1-(propyl-3-sulfonate) 3-methylimidazol(3H)-1-ium phosphotungstate In water at 20℃; for 0.133333h; | |
95% | With Tween 40 In water at 110℃; for 6h; Green chemistry; | |
94% | With Fe/Al-MCM-41 In acetonitrile for 0.166667h; Reflux; | |
94% | With zirconium triflate In ethanol; water at 20℃; for 0.5h; Green chemistry; | |
93% | With potassium hydrogensulfate In ethanol at 20℃; for 0.166667h; | |
93% | With nano-BF3*SiO2 at 20℃; for 0.133333h; Neat (no solvent); | |
90% | With manganese(ll) chloride In ethanol at 20℃; for 0.25h; | |
90% | With ZnO-β-zeolite In ethanol at 20℃; for 0.333333h; | |
90% | With titanium(IV) oxide at 20℃; for 0.183333h; | |
90% | With niobium pentachloride In acetonitrile at 20℃; for 0.25h; | |
90% | With sulfonated rice husk ash at 20℃; for 0.5h; Green chemistry; | General procedure for the synthesis of quinoxaline derivatives General procedure: To a mixture of 1,2-diaminobenzene (1 mmol) and 1,2-dicarbonyl compound (1 mmol), RHA-SO3H (15 mg) was added and the mixture was stirred at room temperature for the appropriate time. The progress of the reaction was monitored by TLC (EtOAc: n-hexane 2:8). After completion of the reaction, ethyl acetate (20 mL) was added to the mixture and the solid catalyst was separated. Then the solvent was evaporated and the resulting solid product was recrystallized from ethanol, producing the pure product in high yields. |
89% | With H3PMo12O40 nanoparticles immobilized on imidazole functionalized core-shell Fe3O4(at)SiO2 nanoparticle In ethanol at 20℃; for 0.333333h; Green chemistry; | 5.1 2.2.4. General procedure for the preparation of quinoxaline derivatives General procedure: To a stirred solution of amine (1 mmol) and carbonyl compounds (1 mmol) in EtOH (5 mL) were added Fe3O4SiO2-imid-PMAn (0.03 g, 0.5 mol%). The progress of the reaction was followed by thin-layer chromatography (TLC). After completion of the reaction, ethyl acetate was added to the solidified mixture and the insoluble catalyst was separated by magnetic field. The filtrate was dried and organic medium was removed with a rotary evaporator under reduced pressure. The crude products were crystallized from ethanol to afford pure products for analytical measurements. |
88% | With Thiamine hydrochloride In ethanol at 20℃; for 0.233333h; | |
88% | With rice husk In water; acetonitrile at 50℃; for 1.5h; Green chemistry; | General procedure for the synthesis of quinoxaline derivatives General procedure: A mixture of 1,2-dicarbonyl compound (1 mmol), o-phenylenediamine (1 mmol) and RiH (0.35 mol %) in H2O/CH3CN (2 mL/2 mL) was stirred at 50 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, and evaporation of the solvents, the reaction solid product was extracted with Et2O (3 × 15 mL). The catalyst was filtered and reused for further runs. Et2O was evaporated and the solid residue recrystallized with ethanol to afford the pure product. The physical and spectral data of the known compounds were in agreement with those reported in the literature [40,43,58,59]. |
87% | With vitamin B1 In methanol at 25℃; for 3h; Sonication; | |
85% | In water; glycerol at 90℃; for 4h; | General procedure for synthesis of quinoxoline derivative (Table 2, entry 1): General procedure: To a stirred solution of o-phenylenediamine (0.1 g, 0.92 mmol) in H2O (2 mL), glycerol (5 ml) was added, and the reaction mixture was heated to 90 °C followed by addition of benzyl (0.2 g, 0.92 mmol). The reaction mixture was stirred vigorously at 90 °C. The progress of reaction was monitored by TLC. When all the starting material had been consumed, the reaction was quenched with water (10 mL) and extracted with ethyl acetate (2 × 10 mL). The organic phase was separated and dried over anhydrous Na2SO4 and evaporated under reduced pressure to give crude product. The pure product was isolated by silica gel column chromatography using (EtOAc/hexane, 1:9) |
85% | In neat (no solvent) at 20℃; for 0.333333h; Green chemistry; | General procedure for the synthesis of quinoxalines under solventless conditions General procedure: A mixture of 1,2-phenylenediamine derivative (1 mmol), 1,2-diketones (1 mmol) and nano SbCl5.SiO2 (62%w/w ) (0.15 g) was stirred at room temperature under solventless condition. The reaction was monitored by TLC (n-hexane:ethyl acetate, 7:3). After completion of the reaction, the mixture was washed with chloroform (2×5 mL) and filtered to recover the catalyst. The solvent was evaporated and the crude product was recrystallized from ethanol (5 mL) to afford pure quinoxaline derivatives. |
85% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With ZrOL2(at)SMNP In ethanol at 25℃; for 0.0333333h; Stage #2: 4-Nitrophenylene-1,2-diamine In ethanol at 60℃; for 1.5h; | General procedure for the synthesis of quinoxalines and pyrido pyrazines General procedure: A mixture of the required 1,2-dicarbonyl (1 mmol) and ZrOL2&SMNP (0.004 g) in ethanol (0.5 ml) was stirred at 25°C for 2 min. Then, the required 1,2-diamine (1.5 mmol) was added to the mixture, which was stirred at 60 °C for the appropriate reaction time. The progress of the reaction was monitored by TLC or GC. After completion of the reaction, the precipitate was dissolved by adding ethanol, and ZrOL2&SMNP was separated by decantation of the reaction mixture in the presence of an external magnet. Most of the product was precipitated purely by concentrating and cooling the ethanolic solution. There maining product was isolated from an excess of 1,2-diamine by plate chromatography eluted with n-hexane-EtOAc (10/2). Structural assignments of the products were based on their 1H and 13C NMR spectra. |
84% | With Polystyrene-Supported AlCl3 In ethanol for 1h; Reflux; | |
83% | With zirconium tetrakis(dodecyl sulfate) In water at 20℃; for 1.83333h; | |
82% | With 2-methylenesuccinic acid In water at 20℃; for 1h; Schlenk technique; Green chemistry; | |
80% | With silica-supported bismuth(III) chloride In methanol at 20℃; for 3h; | 4.1 2.3 General procedure for the acid-catalyzed benzo[N,N]-heterocyclic condensation General procedure: A mixture of arene-1,2-diamine (1.2mmol), 1,2-dicarbonyl (1mmol), and 0.20g of BiCl3/SiO2 (5mol %) was taken in methanol (5mL) and stirred at room temperature for the appropriate reaction time (Scheme 1). After completion of the reaction (monitored by TLC using ethyl acetate/hexane (2:8 v/v) or GC), dichloromethane was added to the reaction mixture and the catalyst was recovered by filtration. The organic medium was removed with rotary evaporator under reduced pressure. The crude products were purified by column chromatography using ethyl acetate/hexane (2:8 v/v) [dichloromethane/ethanol (9:1 v/v) for products 1h-1m] to afford pure products for analytical measurements. The products were identified by comparison of their NMR and mass spectra with authentic samples. |
76% | With silica-supported stannous chloride In methanol at 20℃; for 4h; | |
64% | With 5-sulfosalicylic acid anchored to silica-modified Fe3O4 nanocomposite In ethanol at 60℃; | General procedure for the synthesis of quinoxaline derivatives General procedure: To a mixture of a 1,2-diketone (1.0 mmol) and 1,2-diaminobenzene (1.0 mmol) in ethanol (2.0 mL), Fe3O4(at)SiO2(at)5-SA (20 mg) was added and the mixture was stirred at 60 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, the magnetic catalyst was separated by an external magnet. The products were purified by recrystallization from ethanol or methanol. |
45% | With aluminum oxide at 80℃; for 0.583333h; Neat (no solvent); | |
10% | With α-molybdenum trioxide In ethanol at 25 - 60℃; for 2h; Green chemistry; | |
10% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With zirconium dioxide In ethanol at 25℃; for 0.0333333h; Stage #2: 4-Nitrophenylene-1,2-diamine In ethanol at 60℃; for 4h; | |
10% | With C20H24Cl2N2O2Zr In ethanol at 20℃; for 0.833333h; Green chemistry; | |
With sodium acetate In acetic acid for 20h; Reflux; | General procedure for the synthesis of 2,3-Bis(aryl)-6-nitro-quinoxaline: General Procedure: A mixture of 1,2-diketone, 3,4-diaminonitrobenzene (1.1 equiv.), and sodium acetate (2.0 equiv.) in acetic acid was heated to reflux for 20 h. The resulting dark solution was cooled to room temperature and poured into H2O. The precipitates were collected by vacuum filtration, washed with H2O, and dried under high vacuum overnight. | |
With iodine In dimethyl sulfoxide at 20℃; for 12h; | 4.2 General procedure for the synthesis of 3-diphenylquinoxaline 3a General procedure: A mixture of 2-hydroxy-1, 2-diphenylethanone (1.0mmol) and iodine (25mol%) in DMSO (2mL) was stirred at 100°C under an air atmosphere. TLC monitored the end of the reaction. Then the mixture was cooled to room temperature, and benzene-1,2-diamine (1.0mmol) was added into the mixture and stirred for several hours. TLC monitored the end of the reaction. Then H2O (100mL) was added and the mixture was filtered and extracted with ethyl acetate. The combined organic layer was washed by chilled water, dried by Mg2SO4 for 10min, filtered, and evaporated in vacuo. The product was purified by flash column chromatography on silica gel by petroleum ether and ethyl acetate (20:1). White solid was obtained as 3a (0.25g). | |
With toluene-4-sulfonic acid In dimethyl sulfoxide at 100℃; for 1h; | General procedure for the synthesis of compounds 3 General procedure: A mixture of 1,2-diaryl-2-hydroxyethanone 1 (1.0 mmol) and PTSA (0.5 mmol) in DMSO (2 mL) was heated to 100 °C (TLC monitored). Then the mixture was added in o-diaminobenzene 2 (1 mmol), and stirred for 1 h. Then the mixture was cooled to room temperature, diluted with brine (30 mL), and extracted with dichloromethane twice (2 x 30 mL). The combined organic layers were dried with MgSO4 and the solvent was removed in vacuo to afford a residue. The residue was purified by column chromatography to afford 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 4h; | 8 1,2-bis(4-methoxyphenyl)-ethane-1,2-dione prepared according to example 1 (1.135 g, 4.687 mmol) and then potassium carbonate (3.239 g, 23.4 mmol) are added successively to a solution of tosylate WP33 prepared according to example 6 (3.737 g, 10.3 mmol) in DMF (50 ml). The mixture is stirred at 50° C. for 4 hours. After returning to ambient temperature, the mixture is poured into iced water and extracted several times with ethyl acetate. The recombined organic phases are washed several times with a NaHCO3-saturated solution, then with brine. After drying on MgSO4, filtration and concentration under reduced pressure, the residue obtained is purified by flash chromatography on a silica gel (ethyl acetate, then dichloromethane/methanol 1% to 1.5%) to yield 1.568 g (54%, not optimized) of a yellow oil. δH (300 MHz, CDCl3) 3.36 (s; 6H), 3.51 (m; 4H), 3.51-3.71 (m; 20H), 3.87 (m; 4H), 4.19 (m; 4H), 6.97 (d, J 8.8; 4H), 7.92 (d, J 8.8; 4H); MS (Electrospray) m/z 623 (MH+, 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With ammonium acetate In ethanol at 40℃; for 0.583333h; Sonication; Green chemistry; | 2.4. General procedure for the synthesis of 2,4,5-trisubstituted imidazoles ultrasonic irradiation General procedure: A 25 mL Erlenmeyer flask was charged with benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (0.4 g, 5 mmol), SA-MNPs (0.1 g) and ethanol (10 mL). The reaction flask was located in the ultrasonic bath, where the surface of reactants is slightly lower than the level of the water, and irradiated under 20, 40, 60, 80 and 100% of the power of the ultrasonic bath and the temperature inside the reactor at 40 °C for the period of time (The reaction was monitored by TLC) separately as indicated in Table 4. After the reaction was completed, the catalyst was separated by an external magnet and reused as such for the next experiment. The reaction mixture was concentrated on a rotary evaporator under reduced pressure and the solid product obtained was dissolved in acetone and filtered. The solid product obtained was washed with water and recrystallized from acetone-water 9:1 (v/v) to offer pure product 3a in 98% yield. All products were known and characterized by comparison of their physical and spectra data with those already reported [31]. |
91% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; | |
With ammonium acetate; acetic acid Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With ammonium acetate In ethanol at 40℃; for 0.583333h; Sonication; Green chemistry; | 2-(3-methoxyphenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole (3p). 2-(3-methoxyphenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole (3p). White solid. IR (KBr) (υmax/cm-1): 3430 (N-H), 1608 (C=C), 1519 (C=N), 1246 (C-O); 1H NMR (400 MHz, DMSO-d6): δH 12.50 (s, 1H, NH), 7.64 (d, 1H, J = 8.0 Hz, Ar-H), 7.62 (s, 1H, Ar-H), 7.36-7.46 (m, 5H, Ar-H), 7.00 (d, 2H, J = 8.4 Hz, Ar-H), 6.91 (dd, 1H, J = 8.4, 2.2 Hz, Ar-H), 6.87 (d, 2H, J = 8.4 Hz, Ar-H), 3.82 (s, 3H, OMe), 3.79 (s, 3H, OMe), 3.74 (s, 3H, OMe) ppm; 13C NMR (100 MHz, DMSO-d6): δC 160.0, 158.9, 158.2, 145.1, 136.2, 132.3, 130.2, 130.2, 128.6, 128.2, 127.2, 124.1, 117.0, 115.5, 114.4, 114.3, 110.5, 55.6, 55.5, 55.5 ppm; Anal. Calcd. for C24H22N2O3: C, 74.59; H, 5.74; N, 7.25%. Found: C, 74.58; H, 5.75; N, 7.24%. |
91% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; | |
With ammonium acetate; acetic acid Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; | |
92% | With ammonium acetate at 130℃; for 1h; Neat (no solvent); | |
92% | With ammonium acetate In ethanol at 40℃; for 0.666667h; Sonication; Green chemistry; | 2.4. General procedure for the synthesis of 2,4,5-trisubstituted imidazoles ultrasonic irradiation General procedure: A 25 mL Erlenmeyer flask was charged with benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (0.4 g, 5 mmol), SA-MNPs (0.1 g) and ethanol (10 mL). The reaction flask was located in the ultrasonic bath, where the surface of reactants is slightly lower than the level of the water, and irradiated under 20, 40, 60, 80 and 100% of the power of the ultrasonic bath and the temperature inside the reactor at 40 °C for the period of time (The reaction was monitored by TLC) separately as indicated in Table 4. After the reaction was completed, the catalyst was separated by an external magnet and reused as such for the next experiment. The reaction mixture was concentrated on a rotary evaporator under reduced pressure and the solid product obtained was dissolved in acetone and filtered. The solid product obtained was washed with water and recrystallized from acetone-water 9:1 (v/v) to offer pure product 3a in 98% yield. All products were known and characterized by comparison of their physical and spectra data with those already reported [31]. |
90% | With ammonium acetate; <i>L</i>-proline In methanol at 60℃; for 13h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione; tert butyl 4-formylpiperidine-1-carboxylate With ammonium acetate; acetic acid at 120℃; for 4h; Stage #2: With sodium hydrogencarbonate In water | 69 To a solution of 4,4'-dimethoxybenzil (Reference Example 68) (975 mg, 3.6 mmol) and 1-tert-butoxycarbonylpiperidinecarbaldehyde (Reference Example 67) (769 mg, 3.6 mmol) in acetic acid (40 ml), ammonium acetate (5.6 g 72 mmol) was added. The reaction solution was heated at 120°C for 4 hours with stirring and then cooled to room temperature. The reaction solution was concentrated under a reduced pressure, and saturated aqueous sodium bicarbonate was added to the residue, followed by extraction with chloroform. The organic layer was washed with distilled water, dried over magnesium sulfate, and concentrated under a reduced pressure. The residue was purified by flash chromatography (amine silica gel, chloroform/methanol = 50/1 to 10/1) to give a title compound (910 mg, 2.5 mmol, 69%) as a light yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 1.67-1.78 (2H, m), 1.91 (1H, brs), 2.02-2.04 (2H, m), 2.69-2.74 (2H, m), 2.87-2.95 (1H, m), 3.14-3.17 (2H, m), 3.81 (6H, s), 6.85-6.87 (4H, m), 7.31-7.59 (4H, m), 9.29 (1H, brs). IR (KBr, cm-1): 2938, 2834, 1615, 1539, 1516, 1493, 1444, 1364, 1295, 1248, 1174, 1107, 1034, 970, 834. EI-MS: m/z = 364 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With 2-methylenesuccinic acid In water at 20℃; for 1h; Schlenk technique; Green chemistry; | |
72% | With acetic acid at 30 - 130℃; for 3.5h; | 57 2,3-Bis(4-methoxyphenyl)quinoxaline-6-carbonitrile A solution of 3,4-diaminobenzonitrile (50 mg, 0.30 mmol, 1.00 equiv, 80%) and 1,2-bis(4-methoxyphenyl)ethane-1,2-dione (89 mg, 0.33 mmol, 1.00 equiv) in acetic acid (5 mL) was stirred for 30 min at 30° C. in an oil bath, then at 130° C. for 3 h. The reaction was quenched with 10 mL of water. The solids were collected by filtration and dried in an oven under reduced pressure, yielding 80 mg (72%) of 2,3-bis(4-methoxyphenyl)quinoxaline-6-carbonitrile as a yellow solid. LC-MS (ES, m/z): [M+H]+ calculated for C23H18N3O2: 368. Found: 368. 1H-NMR (300 MHz, CDCl3, ppm): δ 8.698-8.702 (s, 1H), 8.229-8.258 (d, J=8.7 Hz, 1H), 8.108-8.142 (d, J=10.2 Hz, 1H), 7.468-7.515 (s, 4H), 6.957-6.982 (m, 4H), 3.802 (s, 6H). |
71% | With acetic acid for 1h; Reflux; | 31.1 Into a 100-mL round-bottom flask, was placed a solution of l,2-bis(4- methoxyphenyl)ethane-l,2-dione (200 mg, 0.74 mmol, 1.00 equiv) in acetic acid (20 mL), 3,4-diaminobenzonitrile (118.2 mg, 0.89 mmol, 1.20 equiv). The resulting solution was stirred for 1 h at reflux in an oil bath. The reaction was then quenched by the addition of water. The solids were collected by filtration and washed with MeOH. This resulted in 205 mg (71%) of 2,3-bis(4-methoxyphenyl)quinoxaline-6- carbonitrile as a yellow solid.LC-MS-PH: (ES, m/z): 368 [M+H]+ |
71% | Stage #1: 4-cyano-1,2-phenylenediamine; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With acetic acid for 1h; Reflux; Stage #2: With water In acetic acid | 26.1 EXAMPLE 26 2,3-Bis(4-methoxyphenyl)-6-(1H-tetrazol-5-yl)quinoxaline Step 1. 3-Bis(4-methoxyphenyl)quinoxaline-6-carbonitrile A solution of 1,2-bis(4-methoxyphenyl)ethane-1,2-dione (200 mg, 0.74 mmol, 1.00 equiv) in acetic acid (20 mL) and 3,4-diaminobenzonitrile (118.2 mg, 0.89 mmol, 1.20 equiv) was stirred for 1 h at reflux in an oil bath. The reaction was then quenched by the addition of water. The solids were collected by filtration and washed with MeOH. This resulted in 205 mg (71%) of 2,3-bis(4-methoxyphenyl)quinoxaline-6-carbonitrile as a yellow solid.LC-MS (ES, m/z): 368 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With aluminum oxide at 20℃; for 0.166667h; neat (no solvent); | |
95% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In ethyl acetate at 0 - 20℃; for 5h; | |
91% | at 120℃; for 0.666667h; Green chemistry; |
57% | With cobalt(III) 5,10,15,20-tetraarylporphyrin In ethanol; water for 1h; Reflux; | |
for 1h; | 4.1 General procedure for the synthesis of compound 3 (using 2,3-diphenylquinoxaline 3aa as an example) General procedure: A stirred solution of deoxybenzoin 1a (196 mg, 1.0 mmol), CuO (88 mg, 1.1 mmol), and iodine (279 mg, 1.1 mmol) was heated at 100 °C for 4 h in DMSO (3 mL), after the disappearance of the starting material (TLC), 1,2-diamine 2a (324 mg, 3.0 mmol) was added and stirred for another 1 h. Then the reaction mixture was poured into 50 mL brine and the aqueous layer was extracted with EtOAc (3×50 mL). The extract was washed with Na2S2O3 solution, dried over anhydrous Na2SO4 then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether/EtOAc as the eluent to give the expected products 3aa as the yellow solid (240 mg, 85% yield). | |
With iodine In dimethyl sulfoxide at 20℃; for 12h; | 4.2 General procedure for the synthesis of 3-diphenylquinoxaline 3a General procedure: A mixture of 2-hydroxy-1, 2-diphenylethanone (1.0mmol) and iodine (25mol%) in DMSO (2mL) was stirred at 100°C under an air atmosphere. TLC monitored the end of the reaction. Then the mixture was cooled to room temperature, and benzene-1,2-diamine (1.0mmol) was added into the mixture and stirred for several hours. TLC monitored the end of the reaction. Then H2O (100mL) was added and the mixture was filtered and extracted with ethyl acetate. The combined organic layer was washed by chilled water, dried by Mg2SO4 for 10min, filtered, and evaporated in vacuo. The product was purified by flash column chromatography on silica gel by petroleum ether and ethyl acetate (20:1). White solid was obtained as 3a (0.25g). | |
With toluene-4-sulfonic acid In dimethyl sulfoxide at 100℃; for 1h; | General procedure for the synthesis of compounds 3 General procedure: A mixture of 1,2-diaryl-2-hydroxyethanone 1 (1.0 mmol) and PTSA (0.5 mmol) in DMSO (2 mL) was heated to 100 °C (TLC monitored). Then the mixture was added in o-diaminobenzene 2 (1 mmol), and stirred for 1 h. Then the mixture was cooled to room temperature, diluted with brine (30 mL), and extracted with dichloromethane twice (2 x 30 mL). The combined organic layers were dried with MgSO4 and the solvent was removed in vacuo to afford a residue. The residue was purified by column chromatography to afford 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With ammonium acetate at 200℃; for 3h; | General procedure for the preparation of compounds 3a-k A mixture of acenaphthoquinone (1 mmol), the appropriate benzil (1 mmol), and ammonium acetate (4 mmol) was heated at 200 °C for 3 h. The reaction mixture was cooled to room temperature and the product was purified by column chromatography using n-hexane-EtOAc (3:1) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 78% 2: 15% | With samarium; potassium iodide; copper(l) chloride In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; | Typical Procedure for the Self-Condensation of Aromatic Aldehydes General procedure: Benzaldehyde (0.4 mL, 4 mmol) was added to a mixture of Sm powder (0.3 g, 2 mmol), CuCl (0.2 g, 2 mmol), and KI (0.33 g, 2 mmol) in anhydrous tetrahydrofuran (THF, 10 mL) at room temperature under a nitrogen atmosphere with magnetic stirring. After completion of the reaction (about 2 h, monitored by TLC), dilute hydrochloric acid (2 M, 5 mL) was added and the resulting mixture was extracted with ethyl acetate (320 mL). The combined organic layer was washed with brine and saturated sodium thiosulfate solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product were purified with flash chromatography (silica/hexane-ethyl acetate 5:1 v/v) to afford 0.36 g of the corresponding benzoin (2a) with 84% yield. |
1: 52% 2: 9% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 25℃; for 40h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6%; 46%; 12%; 59% | With palladium diacetate; caesium carbonate; In N,N-dimethyl-formamide; at 120℃; for 0.5h;Inert atmosphere; | General procedure: A stirred mixture of bromobenzene (471 mg, 3.0 mmol), <strong>[872-36-6]vinylene carbonate</strong> (86 mg, 1.0 mmol), Pd(OAc)2 (22 mg, 10 mol %), PPh3 (52 mg, 20 mol %), and Cs2CO3 (715 mg, 2.2 mmol) in DMF (1.5 mL) was heated to 120 C for 30 min under nitrogen atmosphere. After aqueous extractive workup and column chromatographic purification process (hexanes/EtOAc, 20:1) benzil was obtained as a pale yellow solid, 170 mg (81% based on <strong>[872-36-6]vinylene carbonate</strong>), along with biphenyl (65 mg, 28% based on bromobenzene) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With ammonium acetate In ethanol at 40℃; for 0.583333h; Sonication; Green chemistry; | 5-[4,5-Bis(4-methoxyphenyl)-1H-imidazol-2-yl]-2-methoxyphenol (3q). 5-[4,5-Bis(4-methoxyphenyl)-1H-imidazol-2-yl]-2- methoxyphenol (3q). Ash-gray solid. IR (KBr) (υmax/cm-1): 3424 (N-H), 3320 (O-H), 1615 (C=C), 1504 (C=N), 1249 (C-O); 1H NMR (400 MHz, DMSO-d6): δH 12.26 (s, 1H, NH), 9.11 (s, 1H, OH), 7.52 (s, 1H, Ar-H), 7.37-7.46 (m, 6H, Ar-H), 6.98 (d, 2H, J = 8.4 Hz, Ar-H), 6.86 (d, 2H, J = 8.4 Hz, Ar-H), 3.80 (s, 3H, OMe), 3.78 (s, 3H, OMe), 3.73 (s, 3H, OMe) ppm; 13C NMR (100 MHz, DMSO-d6): δC 159.1, 158.7, 148.4, 146.9, 145.6, 129.8, 129.2, 128.4, 126.3, 126.0, 123.5, 124.1, 116.8, 114.3, 114.0, 113.2, 112.5, 56.1, 55.5, 55.1 ppm; Anal. Calcd. for C24H22N2O4: C, 71.63; H, 5.51; N, 6.96%. Found: C, 71.61; H, 5.49; N, 6.95%. |
95% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With ammonium acetate In ethanol at 40℃; for 0.583333h; Sonication; Green chemistry; | 2.4. General procedure for the synthesis of 2,4,5-trisubstituted imidazoles ultrasonic irradiation General procedure: A 25 mL Erlenmeyer flask was charged with benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (0.4 g, 5 mmol), SA-MNPs (0.1 g) and ethanol (10 mL). The reaction flask was located in the ultrasonic bath, where the surface of reactants is slightly lower than the level of the water, and irradiated under 20, 40, 60, 80 and 100% of the power of the ultrasonic bath and the temperature inside the reactor at 40 °C for the period of time (The reaction was monitored by TLC) separately as indicated in Table 4. After the reaction was completed, the catalyst was separated by an external magnet and reused as such for the next experiment. The reaction mixture was concentrated on a rotary evaporator under reduced pressure and the solid product obtained was dissolved in acetone and filtered. The solid product obtained was washed with water and recrystallized from acetone-water 9:1 (v/v) to offer pure product 3a in 98% yield. All products were known and characterized by comparison of their physical and spectra data with those already reported [31]. |
90% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With ammonium acetate In ethanol at 40℃; for 0.583333h; Sonication; Green chemistry; | 2.4. General procedure for the synthesis of 2,4,5-trisubstituted imidazoles ultrasonic irradiation General procedure: A 25 mL Erlenmeyer flask was charged with benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (0.4 g, 5 mmol), SA-MNPs (0.1 g) and ethanol (10 mL). The reaction flask was located in the ultrasonic bath, where the surface of reactants is slightly lower than the level of the water, and irradiated under 20, 40, 60, 80 and 100% of the power of the ultrasonic bath and the temperature inside the reactor at 40 °C for the period of time (The reaction was monitored by TLC) separately as indicated in Table 4. After the reaction was completed, the catalyst was separated by an external magnet and reused as such for the next experiment. The reaction mixture was concentrated on a rotary evaporator under reduced pressure and the solid product obtained was dissolved in acetone and filtered. The solid product obtained was washed with water and recrystallized from acetone-water 9:1 (v/v) to offer pure product 3a in 98% yield. All products were known and characterized by comparison of their physical and spectra data with those already reported [31]. |
92% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; | |
167 mg | With ammonium acetate In ethanol at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With ammonium acetate In ethanol at 40℃; for 0.583333h; Sonication; Green chemistry; | 2.4. General procedure for the synthesis of 2,4,5-trisubstituted imidazoles ultrasonic irradiation General procedure: A 25 mL Erlenmeyer flask was charged with benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (0.4 g, 5 mmol), SA-MNPs (0.1 g) and ethanol (10 mL). The reaction flask was located in the ultrasonic bath, where the surface of reactants is slightly lower than the level of the water, and irradiated under 20, 40, 60, 80 and 100% of the power of the ultrasonic bath and the temperature inside the reactor at 40 °C for the period of time (The reaction was monitored by TLC) separately as indicated in Table 4. After the reaction was completed, the catalyst was separated by an external magnet and reused as such for the next experiment. The reaction mixture was concentrated on a rotary evaporator under reduced pressure and the solid product obtained was dissolved in acetone and filtered. The solid product obtained was washed with water and recrystallized from acetone-water 9:1 (v/v) to offer pure product 3a in 98% yield. All products were known and characterized by comparison of their physical and spectra data with those already reported [31]. |
88% | With 5,10,15,20-tetrakis(4-methylphenyl)porphyrinatozinc(II); ammonium acetate In ethanol at 25℃; for 1.33333h; Ultrasound irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione; 2,3-diaminomaleonitrile With sodium azide In dimethyl sulfoxide at 100℃; for 3h; Stage #2: With hydrogenchloride In water; dimethyl sulfoxide | 4.1.1. Typical procedure for the preparation of 3-(1H-tetrazole-5-yl) pyrazine-2-carbonitrile (3a) General procedure: A mixture of oxalaldehyde (1 mmol), 2,3-diaminomaleonitrile (1 mmol), and sodium azide (1.5 mmol) in DMSO (2 mL) was stirred at 100 °C for 3 h. After completion of the reaction confirmed by TLC (eluent: EtOAc/n-hexane, 1:1), the solvent was removed. To the residue was added 10 mL of 2 N HCl with vigorous stirring causing the 3-(1H-tetrazole-5-yl) pyrazine-2-carbonitrile 3a as cream powder (0.16 g, yield 91%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione; 2,3-diaminomaleonitrile With sodium azide In dimethyl sulfoxide at 100℃; for 3h; Stage #2: With hydrogenchloride In water; dimethyl sulfoxide | 4.1.6. Typical procedure for the preparation of 2,3-di(1H-tetrazole-5-yl)pyrazine (5a) General procedure: A mixture of oxalaldehyde (1 mmol) 2,3-diaminomaleonitrile (1 mmol), sodium azide (3 mmol) in DMSO (2 mL) was stirred at 100 °C for 6 h. After completion of the reaction confirmed by TLC (eluent: EtOAc/n-hexane, 1:1), the solvent was evaporated under reduced pressure. To the participate was added 20 mL of 2 N HCl with vigorous stirring causing the 2,3-di(1H-tetrazole-5-yl) pyrazine to precipitate. The precipitate was filtered and dried in a drying oven to furnish the 2,3-di(1H-tetrazole-5-yl) 5a as white powder (0.20 g, yield 93%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In ethanol; water;Reflux; | Step 2. 2,3-Bis-(4-methoxyphenyl)quinoxaline-6-sulfonic acid A solution of 1,2-bis(4-methoxyphenyl)ethane-1,2-dione (400 mg, 1.48 mmol, 1.00 equiv) and <strong>[7474-78-4]3,4-diaminobenzenesulfonic acid</strong> (278 mg, 1.48 mmol, 1.00 equiv) in ethanol/water (1:1, 20 mL) was stirred overnight at reflux in an oil bath. The resulting mixture was concentrated in vacuo, resulting in 500 mg (80percent) of 2,3-bis-(4-methoxyphenyl)quinoxaline-6-sulfonic acid as a brown solid. |
80% | In ethanol; water;Reflux; | A solution of 1,2-bis(4-methoxyphenyl)ethane-1,2-dione (400 mg, 1.48 mmol, 1.00 equiv) and <strong>[7474-78-4]3,4-diaminobenzenesulfonic acid</strong> (278 mg, 1.48 mmol, 1.00 equiv) in ethanol/water (10/10 mL) was stirred overnight at reflux in an oil bath. The resulting mixture was concentrated under vacuum, yielding 500 mg (80percent) of 2,3-bis(4-methoxyphenyl)quinoxaline-6-sulfonic acid as a brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With pyridinium chlorochromate In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere; | General procedure for the preparation of 1,2-diketones. General procedure: To a stirred solution of α-hydroxy ester in dry DCM was added PCC (3 equiv) slowly at 0 °C. Reaction mixture was stirred for the next 2 h at room temperature and was directly poured onto the column using DCM or ethylacetate-hexane as an eluent for purification to furnish 1,2-diketone.1-(1H-Indol-3-yl)propane-1,2-dione (5) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In neat (no solvent) at 20℃; for 1h; Schlenk technique; | |
21% | With oxygen; rose bengal; acetic acid In water at 20℃; for 48h; Irradiation; Schlenk technique; | 1.7 General procedure for synthesis of products (taking 2a as an example) General procedure: A mixture of 1,1-diphenylethylene 1a (36 mg, 0.20 mmol), Acid Red 94 (10 mg, 0.01 mmol), AcOH (6 mg, 0.1 mmol)and H2O (2.0 mL) were added to a 25 mL Schlenk tube. The reaction tube was flushed with O2 for 1.0 minute and then equipped with a O2 balloon. The reaction was stirred for 48 h under 18 W blue LEDs irradiation. Then the resulting mixture was extracted with EtOAc (3×10 mL). The combined organic phase was dried over anhydrous MgSO4, filtered, and all the volatiles were evaporated under reduced pressure. The resultant residue was purified by silica gel column chromatography (eluent: PE (60-90°C) / EtOAc = 20:1) to afford the desired product 2a in 95% yield. |
134 mg | With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride; tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water; toluene; acetonitrile at 20℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With α-molybdenum trioxide In ethanol at 25 - 60℃; for 5h; Green chemistry; | |
87% | With zirconium triflate In ethanol; water at 20℃; for 0.5h; Green chemistry; | |
73% | Stage #1: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With ZrOL2(at)SMNP In ethanol at 25℃; for 0.0333333h; Stage #2: 5-bromo-pyridine-2,3-diamine In ethanol at 60℃; for 1.5h; | General procedure for the synthesis of quinoxalines and pyrido pyrazines General procedure: A mixture of the required 1,2-dicarbonyl (1 mmol) and ZrOL2&SMNP (0.004 g) in ethanol (0.5 ml) was stirred at 25°C for 2 min. Then, the required 1,2-diamine (1.5 mmol) was added to the mixture, which was stirred at 60 °C for the appropriate reaction time. The progress of the reaction was monitored by TLC or GC. After completion of the reaction, the precipitate was dissolved by adding ethanol, and ZrOL2&SMNP was separated by decantation of the reaction mixture in the presence of an external magnet. Most of the product was precipitated purely by concentrating and cooling the ethanolic solution. There maining product was isolated from an excess of 1,2-diamine by plate chromatography eluted with n-hexane-EtOAc (10/2). Structural assignments of the products were based on their 1H and 13C NMR spectra. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With iodine; dimethyl sulfoxide; copper(ll) bromide for 8h; Schlenk technique; Heating; | |
86% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; acetic acid; copper(I) bromide at 100℃; for 2h; | |
85% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(II) bis(trifluoromethanesulfonate) In N,N-dimethyl-formamide at 120℃; | 8 Example 8: Synthesis of 1,2-bis(4-methoxyphenyl)ethyldione 1,3-bis(4-methoxyphenyl)propan-1,3-dione as a starting material, the reaction procedure is as follows: Reaction flask was added 1,3-bis(4-methoxyphenyl)propan-1,3-dione (0.28g, 1mmol), 2,2,6,6-tetramethylpiperidine-N-oxide (0.31g, 2mmol), Copper triflate (0.036g, 0.1mmol) and dimethylformamide (2 ml),120 reaction;TLC until the reaction was followed completely finished;After completion of the reaction the crude product obtained was purified by column chromatography (petroleum ether: ethyl acetate = 40) to give the desired product (yield 85%). |
56% | With pyridine; oxygen; copper(I) bromide In toluene at 100℃; for 18h; Schlenk technique; | |
56% | With pyridine; oxygen; copper(I) bromide In toluene at 100℃; for 24h; | 3): 1,2-Bis(4-methoxyphenyl)ethane-1,2-dione. 3): 1,2-Bis(4-methoxyphenyl)ethane-1,2-dione. The reaction of CuBr (3.6 mg, 0.025 mmol), pyridine (10.0 mg, 0.125 mmol), 1,3-bis(4-methoxyphenyl)propane-1,3-dione 1c (71 mg, 0.25 mmol) in toluene (2 mL), at 100 °C, under O2(1 atm), for 24 h, afforded 38 mg (56%) of 2c. 2c: yellow solid; 1H NMR (CDCl3, 400 MHz): δ = 7.95 (d, J= 8.8 Hz, 4H), 6.97 (d, J= 9.2 Hz, 4H), 3.89 (s, 6H); 13C NMR (CDCl3, 100 MHz): δ = 193.5, 164.9, 132.4, 126.3, 114.3, 55.6 ppm; IR (neat): ν = 3451.8, 2919.2, 1655.7, 1599.8 cm-1; MW (EI): 270.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | Stage #1: 2-<2-(1,3-dioxolanyl)>benzaldehyde; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With ammonium acetate In chloroform at 110℃; for 24h; Sealed tube; Stage #2: With acetic acid In chloroform at 110℃; for 24h; Sealed tube; | |
39% | Stage #1: 2-<2-(1,3-dioxolanyl)>benzaldehyde; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With ammonium acetate In chloroform at 110℃; for 24h; Sealed tube; Stage #2: With acetic acid In chloroform at 110℃; for 24h; Sealed tube; | 5 Synthesis of 1,2-bis(4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl)benzene In a sealed tube container 501 mg (2.81 mmol) of 2-(1,3-dioxolan-2-yl)benzaldehyde, 1.60 g (5.92 mmol) of 4,4'-dimethoxybenzil, 1.21 mg (15.7 mmol) of ammonium acetate and chloroform (8 mL) were added and the mixture was stirred at 110 ° C. for 24 hours. 1 mL of acetic acid was added and stirring was further continued at 110 ° C. for 24 hours. The resulting mixture was neutralized with aqueous ammonia, extracted with chloroform, the organic layer was dried with sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (hexane / ethyl acetate = 1/1) to obtain 701 mg (1.10 mmol) of 1,2-bis(4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl)benzene in 39% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: 4-fluoroaniline With trimethylaluminum In toluene at 120℃; for 2h; Inert atmosphere; Stage #2: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione In toluene at 120℃; for 6h; Inert atmosphere; | N,N'-(p-methoxyphenyl-1,2-ethane)bis(4-fluoroaniline)(formula shown II-c) was prepared as follows: Take two 100mL flask equipped with a reflux condenser, evacuated and replacedthree times with argon, was added 4-fluoroaniline (1.333g, 12mmol), 20 mL of toluene; atroom temperature was slowly added dropwise trimethylaluminum (2.0M, 6.0mL, 12mmol); dropwas completed, moved to 120 in an oil bath at reflux for 2h; cooled to roomtemperature, 4,4'-dimethyl benzil (1.191g, 5mmol), moved to an oil bath at refluxwas continued for 6h; the reaction is complete after washed with 5% sodium hydroxidesolution was quenched with ethyl acetate twice, dried over anhydrous sodium sulfate.After removal of the solvent was recrystallized from ethanol to give 1.740g of yellowsolid, yield 82%. |
Stage #1: 4-fluoroaniline With trimethylaluminum In toluene for 2h; Inert atmosphere; Reflux; Stage #2: 1,2-bis(4-methoxyphenyl)-1,2-ethanedione In toluene at 20℃; for 6h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With lithium 1-naphthalenide In tetrahydrofuran at 0℃; Inert atmosphere; | 2 5.2.2 2.2-Bis(4-methoxyphenyl)ethane-1,2-dione (9) To a solution of naphthalene (23.3 g, 181 mmol) in anhydrous THF (100 mL) was added lithium (1.26 g, 181 mmol) under N2 at room temperature. The mixture was continuously stirred at room temperature for 8 h. The resulting mixture was added dropwise to a solution of 4-dimethoxybenzoic acid (13, 12.5 g, 82.3 mmol) in anhydrous THF (300 mL) at 0 °C and quenched with water upon completion of the addition. After removed the THF and diluted with ethyl acetate (50 mL), the organic layer was separated and the aqueous layer was extracted with ethyl acetate (3 * 30 mL). The combined organic extracts were washed with brine (30 mL) and dried over Na2SO4. After filtered, the solvent was evaporated to obtain a solid which was further recrystallized from ethyl acetate to give pure 9 as a yellow solid (6.80 g, 50%). mp: 134-135 °C; 1H NMR (400 MHz, CDCl3) δ ppm: 7.93 (4H, d, J = 8.40 Hz), 6.95 (4H, d, J = 8.40 Hz), 3.89 (6H, s); 13C NMR (100 MHz, CDCl3) δ ppm: 55.01 (2C), 113.66 (2C), 125.69 (2C), 131.75 (4C), 164.23 (2C), 192.87 (2C); C16H14O4: HRMS: m/z calcd. 280.0892 [M + H]+; found: 271.0965. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: p-aminomethylbenzoic acid; 1,3-dihydroxybenzaldehyde; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With ammonium acetate; acetic acid at 100℃; for 12h; Stage #2: tert-butyl {2-[2-(2-aminoethoxy)ethoxy]ethyl}carbamate With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 6h; Stage #3: With trifluoroacetic acid In dichloromethane at 20℃; for 1.5h; | 98 Example 98 N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-4-((2-(3,5-dihydroxyphenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole-1-yl)methyl)benzamide. 1,3-dihydroxybenzaldehyde (50 mg, 362 µmol), 4-aminomethyl benzoic acid (72 mg, 470 µmol), 4,4'-dimethoxybenzyl (127 mg, 470 µmol) and ammonium acetate (167 mg, 2.2 mmol) were dissolved in acetic acid, heated at 100 °C and stirred for 12 hours. The temperature was decreased to room temperature, and a reaction mixture was diluted with ethyl acetate and then washed with water and a saline solution. An organic layer was dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure. The mixture obtained thereby was purified by flash column chromatography (CH2Cl2:MeOH = 10:1), thereby obtaining a compound with a yield of 73%. The acid obtained as described above (30 mg, 58 µmol), t-butyl 2-(2-(2-aminoethoxy)ethoxy)ethylcarbamate (13 mg, 86 µmol), EDC (12 mg, 75 µmol) and DMAP (2 mg, 17 µmol) were dissolved in DMF, and stirred at room temperature for 6 hours. The reaction mixture was diluted with ethyl acetate, and washed with water and a saline solution. An organic layer was dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure. The obtained mixture was purified by flash column chromatography (CH2Cl2:MeOH = 10:1). A compound obtained thereby was dissolved in 75% TFA-CH2Cl2 and stirred at room temperature for 1.5 hours. A high-volatile material was removed under reduced pressure, and dissolved in CH2Cl2. The resultant solution was washed with water, saturated NaHCO3 and a saline solution. The organic layer was dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The mixture obtained thereby purified by flash column chromatography (CH2Cl2:MeOH = 10:1), thereby obtaining a target compound with a yield of 75%: 1H NMR(CD3OD, 400MHz) δ7.65(d, J=8.0Hz, 2H), 7.35(d, J=8.8Hz, 2H), 7.11(d, J=8.4Hz, 2H), 6.88(d, J=8.8Hz, 2H), 6.85(d, J=8.0Hz, 2H), 6.76(d, J=8.8Hz, 2H), 6.53(s, 2H), 6.35(s, 1H), 5.21(s, 2H), 3.78(s, 3H), 3.73(s, 3H), 3.63-3.53(m, 10H), 2.84-2.82(m, 2H); 13C NMR(CDCl3, 100MHz) δ169.8, 161.5, 160.1, 160.0, 149.5, 142.6, 138.7, 134.6, 133.5, 133.2, 130.2, 129.4, 129.1, 128.6, 128.5, 128.0, 127.9, 127.3, 123.7, 115.4, 114.5, 108.8, 108.9, 104.8, 71.5, 71.3, 70.5, 55.7, 55.6, 47.2, 41.5, 40.8; The obtained value of MALDI-TOF-MS calculated for C37H41N4O7 [M+H]+ 653.2900 was 653.1543. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With acetic acid; for 2.5h;Reflux; | General procedure: Intermediate compound 5 (0.2 g, 1.24 mmol) and benzil 6d (0.26 g, 1.24 mmol) were weighed and dissolved in 20 mL glacial acetic acid. This mixture was refluxed for 2.5hr. The completion of reaction was monitored by TLC. The reaction mixture was cooled and poured into crushed ice. The precipitated product was filtered off and washed with cold water. The product was then purified by column chromatography using hexane: ethyl acetate as mobile phase. The pure fractions obtained were dried and concentrated to obtain white solids of product 7d. (yield 82%, m.p. 110-112 C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With ammonium acetate In acetic acid at 118℃; for 24h; | Typical procedure for preparation of 2-(2-(4,5-diphenyl-1H-imidazol-3-ium-2-yl)phenoxy)acetate (7a) General procedure: A solution of benzil (0.21 g, 1 mmol), 2-(2-formylphenoxy)acetic acid (0.18 g, 1 mmol) and ammonium acetate (excessamount) in AcOH (5 mL) was heated at reflux for 24 h. After completion of the reaction, as indicated by TLC (ethylacetate/n-hexane, 3/1), the mixture was cooled to room temperatureand poured into cold H2Oto precipitate the crude product7a as cream powder (0.32 g, yield 86%); mp 160-163 °C. IR(KBr) cm-1: 3048, 2929, 2848, 1733, 1652, 1600, 1489, 1407.1H NMR (300.13 MHz, DMSO-d6) δ: 3.59-3.98 (1H, bm,NH), 4.01-4.06 (1H, m, NH), 4.89 (2H, s, CH2),7.10-8.21(14H, m, H-Ar). 13C NMR (100.62 MHz, DMSO-d6) δ: 66.6,114.4, 118.9, 122.3, 127.7, 128.2, 128.4, 129.0, 130.4, 133.2,143.4, 154.6, 172.0. Anal. calcd for C23H18N2O3:C, 74.58; H,4.90; N, 7.56; found C, 78.50; H, 4.91; N, 7.46 |
With ammonium acetate In acetic acid for 5h; Reflux; | General procedure for the synthesis of [2-(4,5-diaryl-1H-imidazole-2-yl) phenoxy]acetic acid (4) General procedure: Mixtures of 1,2-diketons (1; 1 mmol) and 2-formylphenoxy acetic acids (2; 1 mmol) and ammonium acetate (3; excess) were heated at refluxed for 5 h in acetic acid. Upon completion of the reaction, checked by TLC, the reaction mixture was poured into ice-water with stirring. The precipitated products were recrystallized from ethanol to give pure products (4). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With selenium(IV) oxide; palladium diacetate In dimethyl sulfoxide at 130℃; for 24h; chemoselective reaction; | General procedure for synthesis of benzil derivatives General procedure: In a clean and dry 20 mL Schlenk tube added 1.2 mmol of diazonium salt, 1 mmol of styrene, 0.5 mol% palladium acetate and 1 mmol selenium dioxide and 2 mL DMSO. Reaction mixture was heated at 130 °C and progress of the reaction was moniterd on TLC and GCMS. After completion of reaction the reaction mass is cooled to room temperature and reaction mass was filtered to remove reduced selenium metal. Then added 5 ml ethyl acetate to filtrate. The filtrate washed with brine 5 ml x 2 times and then with water 10 ml x 1. Organic layer was separated and dried over sodium sulphate. The crude product was purified by column chromatoghraphy (Silica 60-120 mesh) using ether / ethyl acetate (9:1) as eluent to give the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | In neat (no solvent) at 20℃; for 10h; Green chemistry; | 2.1. Preparation of Pyrazine Derivative General procedure: 1 mmol of recrystallised benzil and 2mmol of ethylenediamine were added to a mortar. The mixture was grinded for a few minutes and transferred to a 50 ml round bottom flask and was kept stirring with a magnetic spinning bar for 6 hrs.The reaction was checked by TLC (ethylacetate and pet-ether). The product was extracted by ethylacetate, washed by water and filtered through Na2SO4. Product was purified by column chromatography using Silica-gel. Petroleum ether-Ethylacetate(PE-EA)mixtures were used as eluent. All the products were characterized by IR, 1H NMR and 13C NMR. |
76% | With silica gel In water at 20℃; for 10h; Green chemistry; | Preparation of 2, 3-disubstituted pyrazines Typical procedure General procedure: Ethylenediamine (1 mmol), benzil (1 mmol), and the silica gel (1 g) were mixed in a mortar and the mixture was grinded for a few minutes in the presence of 2-3 drops of water. Finally, the mixture was transferred to a 50 mL round bottom bottle and was kept under magnetic stirrer at room temperature for 6 h. The completion of reaction was monitored by TLC. Ethyl acetate (3×15 ml) was added to the reaction mixture and the extract was filtered through anhydrous Na2SO4. Finally, 2,3-diphenylpyrazine was isolated by column chromatography over silica gel (60-120 mesh) where pet ether and ethyl acetate mixture was used as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In neat (no solvent) at 20℃; for 5.5h; Green chemistry; | 2.1. Preparation of Pyrazine Derivative General procedure: 1 mmol of recrystallised benzil and 2mmol of ethylenediamine were added to a mortar. The mixture was grinded for a few minutes and transferred to a 50 ml round bottom flask and was kept stirring with a magnetic spinning bar for 6 hrs.The reaction was checked by TLC (ethylacetate and pet-ether). The product was extracted by ethylacetate, washed by water and filtered through Na2SO4. Product was purified by column chromatography using Silica-gel. Petroleum ether-Ethylacetate(PE-EA)mixtures were used as eluent. All the products were characterized by IR, 1H NMR and 13C NMR. |
73% | With silica gel In water at 20℃; for 5.5h; Green chemistry; | Preparation of 2, 3-disubstituted pyrazines Typical procedure General procedure: Ethylenediamine (1 mmol), benzil (1 mmol), and the silica gel (1 g) were mixed in a mortar and the mixture was grinded for a few minutes in the presence of 2-3 drops of water. Finally, the mixture was transferred to a 50 mL round bottom bottle and was kept under magnetic stirrer at room temperature for 6 h. The completion of reaction was monitored by TLC. Ethyl acetate (3×15 ml) was added to the reaction mixture and the extract was filtered through anhydrous Na2SO4. Finally, 2,3-diphenylpyrazine was isolated by column chromatography over silica gel (60-120 mesh) where pet ether and ethyl acetate mixture was used as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With ammonium acetate In ethanol at 78℃; Green chemistry; | General procedure General procedure: A mixture of 1,2-diketone (0.5 mmol), aldehyde (0.5 mmol),ammonium acetate (1.5 mmol) and Fe3O4g-C3N4 (20 mg)in ethanol (1 mL) was heated at 78 °C with stirring for120-200 min. After the completion of the reaction, ethanolwas added and the Fe3O4g-C3N4 was separated magneticallyusing a bar magnet. The reaction mixture was allowedto cool to room temperature to recrystallize from ethanolto get the pure final product. All compounds were knownand characterized on the basis of their melting point and bycomparison with those reported in the literature. |
15 %Spectr. | Stage #1: 4-bromo-benzaldehyde; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With titanium(IV); ammonium acetate at 100℃; for 1h; Molecular sieve; Stage #2: In toluene at 100℃; for 10h; Molecular sieve; | General Procedure for the One-Pot Synthesis of 2,4,5-Triaryl-1H-imidazoles General procedure: A mixture of benzil (1 mmol, 0.21 g), aldehyde (1 mmol), ammonium acetate (2.2 mmol, 0.17 g), and Ti4+/4A (0.1 g) wasstirred in a 10 mL flask at 100 °C. After 1 h toluene (1 mL) was added because the precipitated product impeded stirring of the melt. The stirring was continued, and progress of the reaction was monitored by TLC. After completion (10 h), the mixture was cooled to room temperature, diluted with acetone (10 mL), any solid was filtered off, and the filtrate was evaporated. The product was purified by recrystallization from ethanol. A mixture of benzil (1 mmol, 0.21 g), aldehyde (1 mmol), ammonium acetate (2.2 mmol, 0.17 g), and Ti4+/4A (0.1 g) was stirred in a 10 mL flask at 100 °C. After 1 h toluene (1 mL) was added because the precipitated product impeded stirring of the melt. The stirring was continued, and progress of the reaction was monitored by TLC. After completion (10 h), the mixture was cooled to room temperature, diluted with acetone (10 mL), anysolid was filtered off, and the filtrate was evaporated. Theproduct was purified by recrystallization from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With sodium hexamethyldisilazane In tetrahydrofuran; toluene at 20℃; for 0.5h; Inert atmosphere; | General procedure for the synthesis of 1,2-bis(3,5-dimethoxyphenyl)-3-(4- (2-(aminoalkyl-1-yl)ethoxy) phenyl)prop-2-en-1-ones (17a-f) and 1,2-bis(4-methoxy-phenyl)-3-(4-(2-(aminoalkyl-1-yl)ethoxy) phenyl)prop-2-en-1-ones (18a-f) To a solution of oxybenzoic acid substituted by methyl (15 or 16) (3.02 mmol) and diphenyl{4-[2-(aminoalkyl-1-yl)ethoxy]benzyl}phosphine oxide (3.02 mmol) in anhydrous toluene (100 mL), NaHMDS (2 M, 6.05 mmol) in THF was added under N2 at room temperature. The reaction mixture was quenched with water after 0.5 h stirring. The reaction mixture was concentrated and then diluted with ethyl acetate. The organic layer was washed with water (30 mL) and brine (30 mL), dried over Na2SO4, filtered, and evaporated. The obtained residue was further purified by silica gel column chromatography (0-10% ethyl acetate/hexanes) to give the desired product as yellowish oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With sodium hexamethyldisilazane In tetrahydrofuran; toluene at 20℃; for 0.5h; Inert atmosphere; | General procedure for the synthesis of 1,2-bis(3,5-dimethoxyphenyl)-3-(4- (2-(aminoalkyl-1-yl)ethoxy) phenyl)prop-2-en-1-ones (17a-f) and 1,2-bis(4-methoxy-phenyl)-3-(4-(2-(aminoalkyl-1-yl)ethoxy) phenyl)prop-2-en-1-ones (18a-f) To a solution of oxybenzoic acid substituted by methyl (15 or 16) (3.02 mmol) and diphenyl{4-[2-(aminoalkyl-1-yl)ethoxy]benzyl}phosphine oxide (3.02 mmol) in anhydrous toluene (100 mL), NaHMDS (2 M, 6.05 mmol) in THF was added under N2 at room temperature. The reaction mixture was quenched with water after 0.5 h stirring. The reaction mixture was concentrated and then diluted with ethyl acetate. The organic layer was washed with water (30 mL) and brine (30 mL), dried over Na2SO4, filtered, and evaporated. The obtained residue was further purified by silica gel column chromatography (0-10% ethyl acetate/hexanes) to give the desired product as yellowish oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: dimethyl 2,2'-(acetylazanediyl)diacetate; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With sodium methylate In methanol at 90℃; for 2h; Stage #2: With water In methanol at 90℃; for 1h; | 1.2.33,4-bis(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid (7a). 4,4’-dimethoxybenzil (1.43 g, 5.29 mmol) was added into a solution dimethyl 2,2'-(acetylazanediyl)diacetate5(3.22 g, 15.87 mmol) in methanol (15 ml). The reaction mixture was refluxed for 2h at 90°C. Distilled water (20 ml) was added and the reaction was continued for 1h. The reaction solution was cooled to room temperature and extracted with ethyl acetate. The aqueous phase was adjusted to pH=1 with 6 M HCl, and then aqueous phase was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by recrystallization from ethyl acetate/n-hexane to give the compound7a(1.73 g, 89%yield) as a yellow solid.1H NMR (500 MHz, DMSO) δ 6.95 (d,J= 8.4 Hz, 4H), 6.73 (d,J= 8.5 Hz, 4H), 3.69 (s, 6H). HRMS (ESI) (m/z):calcdfor C20H17NO9[M-H]- 366.0978, found. 366.0978. |
89% | Stage #1: dimethyl 2,2'-(acetylazanediyl)diacetate; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With sodium methylate In methanol at 90℃; for 2h; Stage #2: With water at 90℃; for 1h; | 3 Preparation of compound 4 4,4'-p-methoxyphenol ester (1.43 g, 5.29 mmol) and compound 3 (3.22 g, 15.87 mmol) were dissolved in 15 ml of methanol, and sodium methoxide (20 ml, 5.4 M, 105.80 mmol) was added dropwise at 90 ° C Reflux for 2h, add 20ml of deionized water, and continue stirring at 90 ° C for 1h. After stopping the reaction, return to room temperature, extract with ethyl acetate / water, adjust the aqueous phase to pH = 1 with 6M HCl, extract twice with ethyl acetate / water, rinse the ethyl acetate phase with saturated sodium chloride solution, and then dry it with water. Dry over sodium sulfate and concentrate by rotary evaporation. The crude product was recrystallized from ethyl acetate / n-hexane to give Compound 4 (1.73 g, 89%) as a white solid. |
73% | Stage #1: dimethyl 2,2'-(acetylazanediyl)diacetate; 1,2-bis(4-methoxyphenyl)-1,2-ethanedione With sodium methylate In methanol at 90℃; for 0.5h; Stage #2: With water at 90℃; for 0.5h; | 1.3.4. 3,4-Bis(4-methoxyphenyl)-1H-pyrrole-2,5-dicarboxylic acid (5) Yellow solid compound 5 was synthesized as our previous description[29]. Dimethyl 2,2'-(acetylazanediyl)diacetate 4 (6.98 g, 34.35 mmol) and 4,4’-dimethoxybenzil (3.096 g, 11.45 mmol) was dissolved in methanol (30 mL). After the mixture was refluxed for 0.5 h at 90 °C, distilled water (30 mL) was added into the solution and the reaction was continued for 0.5 h. After the solution was cooled and extracted, the aqueous phase was adjusted to pH=1 using 6 mol/L HCl. The aqueous phase was extracted again for collecting the organic phase. The crude product was purified by recrystallization via ethyl acetate/n-hexane to give the compound 5 (3.07 g, 73 %). 1H-NMR (500 MHz, DMSO-d6) δ 6.95 (d, J = 8.4 Hz, 4H), 6.73 (d, J = 8.5 Hz, 4H), 3.69 (s, 6H). HRMS (m/z) [M-H]-calcd for C20H16NO9 366.1056 found 366.0978. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With tris-(dibenzylideneacetone)dipalladium(0); copper(I) thiophene-2-carboxylate; 4,4'-Dimethoxy-2,2'-bipyridin; potassium carbonate; sodium sulfate In N,N-dimethyl-formamide at 45℃; Inert atmosphere; | 34 Synthesis of compound 3i: Ethyl p-methoxybenzoylformate (0.1 mmol), p-methoxybenzoic anhydride (0.1 mmol, 1.0 equiv), Pd2dba3 (0.0025 mmol, 2.5 mol%), 4,4'-dimethoxy Base-2,2'-bipyridyl (0.01 mmol, 10 mol%), cuprous thiophene-2-carboxylate (0.1 mmol, 1.0 equiv), K2CO3 (0.15 mmol, 1.5 equiv) and anhydrous Na2SO4 (0.15 mmol, 1.5 equiv) Adding to the reaction tube in which the magnet is placed, evacuating the nitrogen three times, adding DMF (1 mL), heating the reaction system to 45 ° C overnight, and detecting the plate, after the complete conversion of the ethyl benzoylformate, the reaction is carried out. The system was cooled to room temperature, extracted with water and quenched with ethyl acetate, dried over anhydrous Na2SO?After removing the organic solvent by a rotary evaporator, the column chromatography was carried out by silica gel column chromatography to afford the desired dibenzoyl compound 3i (yield: 66%) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 5,6-bis(5-methoxythiophen-2-yl)pyrazine-2,3-dicarbonitrile; triethyl phosphite In 1,2-dichloro-ethane at 20℃; for 48h; Schlenk technique; Inert atmosphere; Irradiation; Green chemistry; | |
43% | With 5,6-bis(5-methoxythiophen-2-yl)pyrazine-2,3-dicarbonitrile; triethyl phosphite In 1,2-dichloro-ethane at 20℃; for 48h; Schlenk technique; Inert atmosphere; Irradiation; | 5 Example 5 Preparation of ethyl 2,2-bis (3-methoxyphenyl) acetate (2e): Specific synthesis steps and characterization: In a 10 ml Schlenk tube, dissolve benzyl compound 1e (27 mg, 0.1 mmol, 1.0 equiv.) and P(OEt)3 (33.2 mg, 0.2 mmol, 2.0 equiv.) in DCE (1.0 ml), add EtOH (11.7 μL, 0.2 mmol, 2.0 equiv.) and photocatalyst DPZ (0.0354 mg, 0.1 μmol), irradiate 3W LED (450 nm) at room temperature and stir the reaction for 48 hours. TLC detection reaction is complete. The reaction solution was concentrated under reduced pressure, the residue was separated by silica gel column chromatography (volume ratio, the same below, PE: EA = 20: 1) to obtain diaryl acetate compound 2e, 13 mg, 43%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With water-d2; zinc trifluoromethanesulfonate; zinc In 1,4-dioxane at 90℃; for 1h; Inert atmosphere; Schlenk technique; Green chemistry; | |
92% | With iron(II) triflate; manganese; water-d2 In tert-butyl methyl ether at 80℃; Inert atmosphere; Glovebox; | 6 In an anhydrous and oxygen-free glove box under argon atmosphere,Add Fe(OTf)2(0.002mmol),Mn (1.0 mmol) and 4-methoxy benzil (0.2 mmol) were sequentially added to the reaction tube 10mL,Then add 2ml methyl tert-butyl ether,Then add heavy water (0.2mmol) and send it out of the glove box.The reaction was carried out in an oil bath at 80°C, and the progress of the reaction was detected by TLC monitoring and I2 color development.After the reaction is completed, it is concentrated and passed through the column with silica gel to obtain the deuterated benzoin compound as a white solid.The yield was 92%, and the deuterium incorporation rate was 97%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With ammonium acetate In neat (no solvent) at 110℃; for 0.166667h; Microwave irradiation; Green chemistry; | 2.2.1. General procedure for the synthesis of 2,4,5-trisubstituted imidazole derivatives (3a-c) General procedure: The mixture of 4,4′-dimethoxybenzil (1 mmol), aromatic aldehyde (1 mmol), and ammonium acetate (2 mmol) were transferred to a clean and dry mortar, triturated to form a uniform mixture. The resulting mixture was then transferred to a 10 mL microwave vessel and it was heated at 110 °C using microwave irradiation (300 W) for 10 min. The reaction was monitored by TLC (hexane: ethyl acetate 7:3 v/v) and the products were allowed to cool to room temperature. The resulting residue was directly purified by column chromatography using hexane: ethyl acetate 7:3 v/v as eluent. 2.2.2. Synthesis of 4-(4,5-bis(4-methoxyphenyl)-1H-imidazol-2-yl)phenol (3a, IM1) mp.: 271 °C. Anal.calc. For C23H20N2O3: C, 74.18; H, 5.41; N, 7.52. found: C, 74.06; H, 5.35; N, 7.43. 1H NMR (400 MHz, DMSO-d6) δ: 3.73(s, 6H, (-OCH3)2), 5.22 (s, 1H, -OH), 7.33-7.75 (m, 12H, Ar-H), 12.32 (s, 1H, -NH).MS, m/z: 373 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With ammonium acetate In neat (no solvent) at 110℃; for 0.166667h; Microwave irradiation; Green chemistry; | 2.2.1. General procedure for the synthesis of 2,4,5-trisubstituted imidazole derivatives (3a-c) General procedure: The mixture of 4,4′-dimethoxybenzil (1 mmol), aromatic aldehyde (1 mmol), and ammonium acetate (2 mmol) were transferred to a clean and dry mortar, triturated to form a uniform mixture. The resulting mixture was then transferred to a 10 mL microwave vessel and it was heated at 110 °C using microwave irradiation (300 W) for 10 min. The reaction was monitored by TLC (hexane: ethyl acetate 7:3 v/v) and the products were allowed to cool to room temperature. The resulting residue was directly purified by column chromatography using hexane: ethyl acetate 7:3 v/v as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With glacial acetic acid at 100℃; for 12h; Inert atmosphere; | 2.1.5. Preparation of compound HBO To a stirred solution of compound 2 (0.26 g, 1 mmol) in acetic acid (40 mL) was added 1,2-bis(4-methoxyphenyl)ethane-1,2-dione (0.27 g, 1 mmol) at room temperature. The reaction mixture was stirred at 100 °C under N 2 atmosphere for 12 h. Evaporation of the acetic acid under reduced pressure and the residue was treated with water (50 mL), extracted twice with CH 2 Cl 2 (50 mL ×2). The combined organic layers were washed twice with water and once with brine, dried over anhydrous magnesium sulfate. After removing the solvent under reduced pressure, the residue was pu- rified by chromatography using hexane/EA (30/1, v/v) as an eluent to yield compound HBO as a yellow solid (0.46 g, 93%). 1 H NMR (600 MHz, CDCl 3 ) 8.80 (d, J = 6.0 Hz, 4H), 7.91 (s, 2H), 7.80 (d, J = 6.0 Hz, 4H), 7.58 (d, J = 8.8 Hz, 4H), 6.88 (d, J = 8.8 Hz, 4H), 3.86 (s, 6H). 13 C NMR (150 MHz, CDCl 3 ) 160.62, 151.79, 149.46, 145.85, 138.04, 137.89, 131.38, 131.10, 129.36, 125.56, 113.84, 55.33. Anal. calcd for C 32 H 24 N 4 O 2 : C, 77.40; H, 4.87; N, 11.28; found: C, 77.36; H, 4.90; N, 11.26. |
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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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