* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 465 - 473
[2] Journal of the American Chemical Society, 1952, vol. 74, p. 1580,1582
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 1, p. 253 - 263
2
[ 1004-76-8 ]
[ 134-81-6 ]
[ 14892-97-8 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1945, vol. <5> 12, p. 78,82
3
[ 1668-10-6 ]
[ 134-81-6 ]
[ 18591-57-6 ]
Yield
Reaction Conditions
Operation in experiment
91.1%
Stage #1: With sodium hydroxide In methanolReflux; Inert atmosphere Stage #2: With hydrogenchloride In methanol; water at 0 - 25℃; for 0.5 h;
Benzil (62.0 g, 0.29 mol), aminoacetamide hydrochloride (35.37 g, under nitrogen)0.32 mol) and NaOH (23.2 g, 0.58 mol) were sequentially added to 500 mL of methanol solvent, and heated under reflux for 3 to 4 h, passed through LC-The MS monitors the reaction and the starting material reacts completely. The reaction solution was cooled to 0-5 ° C, then 12 N HCl (38 mL) solution was added dropwise, and in the roomAfter stirring the reaction solution for 30 minutes under temperature, 30 g of sodium hydrogencarbonate and 350 mL of water were added, and the reaction solution was filtered, water (20 mL) and methanol.(20 mL) The solid was washed separately and dried in vacuo to give 65.5 g of 3-methyl-2-hydroxyquinoxaline as a white solid.91.1percent,
89%
With hydrogenchloride; sodium hydroxide; potassium carbonate In methanol; chloroform; water; ethyl acetate
Step 1: Synthesis of 5,6-diphenylpyrazin-2-ol First, 4.2 g (20 mmol) of benzil, 2.21 g (20 mmol) of glycinamide hydrochloride, and 40 mL of methanol were put into a three-neck flask equipped with a reflux pipe, the air in the flask was replaced with nitrogen, the mixture was refluxed, an aqueous solution of 1.6 g (40 mmol) of sodium hydroxide in 3.2 mL of water was added, and the reflux was continued for 3 hours. Then, stirring was performed until the temperature of the flask was returned to room temperature. After that, 2.5 mL of 12M concentrated hydrochloric acid, 2 g of potassium bicarbonate, and 25 mL of water were added to this mixture, and filtration was performed. The obtained residue was dried at 100° C. under reduced pressure and purified by silica gel column chromatography using chloroform and ethyl acetate in a 5:2 ratio as a developing solvent. The solvent in the solution was distilled off and the resulting residue was recrystallized with hexane; thus, 3.04 g of a yellow solid, which was an objective substance, was obtained in a yield of 89percent. The synthesis scheme of Step 1 is shown in (c-1) below.
82.7%
Stage #1: at 0 - 5℃; for 0.75 h;
A solution of 95 gm methanol is 500 ml water was added slowly at 0-5 °C to a solution of (0084) 52.5 gm glycinamide hydrochloride in 600 ml methanol and then stirred at same temperature for 45 minutes. To the reaction mixture was then added 100 gm benzil and maintained under stirring for 4-5 hrs and then neutralized with 185 ml cone, hydrochloric acid to obtain solid. The solid obtained was washed with 400 ml water and dried to obtain (0085) 97.6 gm 2-hydroxy-5,6-diphenylpyrazine. Yield: 82.70 percent.
79%
With hydrogenchloride; sodium hydroxide; potassium carbonate In methanol; water; toluene
Step 1: Synthesis of 5,6-diphenylpyrazin-2-ol First, 21.0 g (100 mmol) of benzil, 13.3 g (120 mmol) of glycinamide hydrochloride, 9.6 g (240 mmol) of sodium hydroxide, and 500 mL of methanol were put into a 1-L three-neck flask, and the air in the flask was replaced with nitrogen. This mixture was heated for reflux for approximately 3 hours. Then, the temperature of the flask was returned to room temperature, 12.5 mL of 12 M concentrated hydrochloric acid was added to this mixture, and stirring was performed for approximately 30 minutes. Then, 10 g of potassium bicarbonate and 125 mL of water were added. Filtration was performed to give a solid, and the solid was washed with water and methanol in this order. The resulting residue was dried at 100° C. under reduced pressure and recrystallized with 50 mL of toluene to give 19.5 g of a yellow solid, which was an objective substance, in a yield of 79percent. The synthesis scheme of Step 1 is shown in (b-1).
79%
With sodium hydroxide In methanol for 3 h; Reflux; Inert atmosphere
First, 21.0 g (100 mmol) of benzil, 13.3 g (120 mmol) of glycinamide hydrochloride, 9.6 g (240 mmol) of sodium hydroxide, and 500 mL of methanol were put into a 1-L three-neck flask, and the air in the flask was replaced with nitrogen. This mixture was heated for reflux for approximately 3 hours. Then, the temperature of the flask was returned to room temperature, 12.5 mL of 12 M concentrated hydrochloric acid was added to this mixture, and stirring was performed for approximately 30 minutes. Then, 10 g of potassium bicarbonate and 125 mL of water were added. Filtration was performed to give a solid, and the solid was washed with water and methanol in this order. The resulting residue was dried at 100° C. under reduced pressure and recrystallized with 50 mL of toluene to give 19.5 g of a yellow solid, which was an objective substance, in a yield of 79percent. The synthesis scheme of Step 1 is shown in (b-1).
Reference：
[1] Patent: CN108623541, 2018, A, . Location in patent: Paragraph 0049-0051; 0069-0072; 0089-0091; 0108-0110; 0127
[2] Patent: US2015/147840, 2015, A1, . Location in patent: Page/Page column
[3] Patent: WO2017/60827, 2017, A1, . Location in patent: Page/Page column 11
[4] Patent: US2015/147840, 2015, A1, . Location in patent: Page/Page column
[5] Patent: US2016/108006, 2016, A1, . Location in patent: Paragraph 0173-0175
[6] European Journal of Organic Chemistry, 2005, # 5, p. 847 - 853
4
[ 1668-10-6 ]
[ 134-81-6 ]
[ 457099-23-9 ]
[ 18591-57-6 ]
Yield
Reaction Conditions
Operation in experiment
80%
With sodium hydroxide In methanol
Step 1: 2-Hydroxy-5,6-diphenylpyrazine. To a stirred suspension of glycinamide hydrochloride (1.1 gm, 10 mmol) in 20 mL MeOH at 0° C. was added 20percent NaOH (10 mL, 50 mmol). A clear solution formed and was treated slowly portionwise with benzil (2.1 gm, 10 mmol) as a solid. The yellow solution was stirred at 0° C. for 2 hours and then neutralized to approximately pH=7 with concentrated HCl. The bright yellow color disappeared and a tan precipitate formed. The material was isolated by filtration with MeOH and triturated with EtOAc to give 2-hydroxy-5,6-diphenylpyrazine (2 gm, 80percent). 1H-NMR (400 MHz, CDCl3) δ8.24 (s, 1H), 7.42-7.31 (m, 4H), 7.39-7.21 (m, 6H).
Reference：
[1] Patent: US2003/69284, 2003, A1,
5
[ 134-81-6 ]
[ 598-41-4 ]
[ 18591-57-6 ]
Reference：
[1] Journal of Medicinal Chemistry, 2016, vol. 59, # 1, p. 253 - 263
6
[ 67-56-1 ]
[ 623-11-0 ]
[ 134-81-6 ]
[ 598-41-4 ]
[ 18591-57-6 ]
Reference：
[1] Journal of the American Chemical Society, 1949, vol. 71, p. 78,79, 80
7
[ 64-17-5 ]
[ 25854-39-1 ]
[ 134-81-6 ]
[ 107-29-9 ]
[ 65-85-0 ]
Reference：
[1] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1927, vol. 184, p. 36[2] Bulletin of the Chemical Society of Japan, 1927, vol. 2, p. 204
8
[ 112980-86-6 ]
[ 134-81-6 ]
[ 4404-98-2 ]
[ 26939-18-4 ]
[ 84110-40-7 ]
Reference：
[1] Russian Journal of Organic Chemistry, 1997, vol. 33, # 1, p. 127 - 128
With indium; acetic acid; In toluene; at 80℃; for 4.5h;Inert atmosphere;
General procedure: 4.2. General procedure for the indium-mediated reductivecyclization of 2-nitroanilines to prepare quinoxalines A mixture of the 2-nitroaniline derivative (1.0 mmol), dione (1.0or 2.0 mmol), indium (0.574 g, 5.0 mmol), and acetic acid (0.300 g,5 mmol or 0.600 g,10 mmol) or indium chloride (0.221 g,1 mmol or0.265 g,1.2 mmol) in methanol (5 mL) or toluene (5 mL) was stirredat 50 C, 80 C, or reux under a nitrogen atmosphere. After com-pletion of the reaction, the reaction mixture was diluted with ethylacetate (30 mL), ltered through Celite, and the ltrate was pouredinto 10% NaHCO3 (30 mL) and extracted with ethyl acetate(30 mL3). The combined organic extracts were dried over MgSO4,ltered, and concentrated. The residue was eluted with ethyl ace-tate/hexane (v/v10/90) through a silica gel column to give thecorresponding pure quinoxaline. Quinoxaline structures werecharacterized by 1H NMR, 13C NMR, FTIR, and GCeMS, and weremostly known compounds. For unknown compounds, elementalanalysis data were additionally obtained. 4.2.1. 2,3-Dimethylquinoxaline (5).19,31aef Yield 87%. Yellow solid,mp 109e110 C (lit.31f mp 105 C). TLC (10% ethyl acetate/hexane) Rf0.30; 1H NMR (400 MHz, CDCl3) d 7.91 (dd, 2H, J6.3, 3.5 Hz), 7.59(dd, 1H, J6.3, 3.5 Hz), 2.66 (s, 6H); 13C NMR (100 MHz, CDCl3)d 153.4, 141.0, 128.7, 128.2, 23.1; IR (KBr) 3109, 3078, 3030, 2995,2953, 2914, 1490, 1398, 1164 cm1;GCeMS m/z (rel intensity) 158(M, 99), 117 (100), 76 (28), 50 (12).
Benzil (62.0 g, 0.29 mol), aminoacetamide hydrochloride (35.37 g, under nitrogen)0.32 mol) and NaOH (23.2 g, 0.58 mol) were sequentially added to 500 mL of methanol solvent, and heated under reflux for 3 to 4 h, passed through LC-The MS monitors the reaction and the starting material reacts completely. The reaction solution was cooled to 0-5 ° C, then 12 N HCl (38 mL) solution was added dropwise, and in the roomAfter stirring the reaction solution for 30 minutes under temperature, 30 g of sodium hydrogencarbonate and 350 mL of water were added, and the reaction solution was filtered, water (20 mL) and methanol.(20 mL) The solid was washed separately and dried in vacuo to give 65.5 g of 3-methyl-2-hydroxyquinoxaline as a white solid.91.1percent,
89%
With hydrogenchloride; sodium hydroxide; potassium carbonate; In methanol; chloroform; water; ethyl acetate;
Step 1: Synthesis of 5,6-diphenylpyrazin-2-ol First, 4.2 g (20 mmol) of benzil, 2.21 g (20 mmol) of glycinamide hydrochloride, and 40 mL of methanol were put into a three-neck flask equipped with a reflux pipe, the air in the flask was replaced with nitrogen, the mixture was refluxed, an aqueous solution of 1.6 g (40 mmol) of sodium hydroxide in 3.2 mL of water was added, and the reflux was continued for 3 hours. Then, stirring was performed until the temperature of the flask was returned to room temperature. After that, 2.5 mL of 12M concentrated hydrochloric acid, 2 g of potassium bicarbonate, and 25 mL of water were added to this mixture, and filtration was performed. The obtained residue was dried at 100° C. under reduced pressure and purified by silica gel column chromatography using chloroform and ethyl acetate in a 5:2 ratio as a developing solvent. The solvent in the solution was distilled off and the resulting residue was recrystallized with hexane; thus, 3.04 g of a yellow solid, which was an objective substance, was obtained in a yield of 89percent. The synthesis scheme of Step 1 is shown in (c-1) below.
82.7%
A solution of 95 gm methanol is 500 ml water was added slowly at 0-5 °C to a solution of (0084) 52.5 gm glycinamide hydrochloride in 600 ml methanol and then stirred at same temperature for 45 minutes. To the reaction mixture was then added 100 gm benzil and maintained under stirring for 4-5 hrs and then neutralized with 185 ml cone, hydrochloric acid to obtain solid. The solid obtained was washed with 400 ml water and dried to obtain (0085) 97.6 gm 2-hydroxy-5,6-diphenylpyrazine. Yield: 82.70 percent.
79%
With hydrogenchloride; sodium hydroxide; potassium carbonate; In methanol; water; toluene;
Step 1: Synthesis of 5,6-diphenylpyrazin-2-ol First, 21.0 g (100 mmol) of benzil, 13.3 g (120 mmol) of glycinamide hydrochloride, 9.6 g (240 mmol) of sodium hydroxide, and 500 mL of methanol were put into a 1-L three-neck flask, and the air in the flask was replaced with nitrogen. This mixture was heated for reflux for approximately 3 hours. Then, the temperature of the flask was returned to room temperature, 12.5 mL of 12 M concentrated hydrochloric acid was added to this mixture, and stirring was performed for approximately 30 minutes. Then, 10 g of potassium bicarbonate and 125 mL of water were added. Filtration was performed to give a solid, and the solid was washed with water and methanol in this order. The resulting residue was dried at 100° C. under reduced pressure and recrystallized with 50 mL of toluene to give 19.5 g of a yellow solid, which was an objective substance, in a yield of 79percent. The synthesis scheme of Step 1 is shown in (b-1).
79%
With sodium hydroxide; In methanol; for 3h;Reflux; Inert atmosphere;
First, 21.0 g (100 mmol) of benzil, 13.3 g (120 mmol) of glycinamide hydrochloride, 9.6 g (240 mmol) of sodium hydroxide, and 500 mL of methanol were put into a 1-L three-neck flask, and the air in the flask was replaced with nitrogen. This mixture was heated for reflux for approximately 3 hours. Then, the temperature of the flask was returned to room temperature, 12.5 mL of 12 M concentrated hydrochloric acid was added to this mixture, and stirring was performed for approximately 30 minutes. Then, 10 g of potassium bicarbonate and 125 mL of water were added. Filtration was performed to give a solid, and the solid was washed with water and methanol in this order. The resulting residue was dried at 100° C. under reduced pressure and recrystallized with 50 mL of toluene to give 19.5 g of a yellow solid, which was an objective substance, in a yield of 79percent. The synthesis scheme of Step 1 is shown in (b-1).
5,6-diphenyl-pyrazine-2-carboxylic acid methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Example 93 Methyl 5,6-Diphenyl-pyrazine-2-carboxylate (93). To a solution of benzyl (500 mg, 2.38 mmol) and 2,3-diaminoproprionic acid monohydro chloride (334 mg, 2.38 mmol) in MeOH (10 ml) was added NaOH (380 mg, 9.51 mmol) at room temperature. After the mixture was refluxed for 6 hours, it was cooled down in an ice-bath, conc. H2SO4 (1 ml) was added dropwise and the whole mixture was stirred under reflux for 3 hours. MeOH was removed and the residue was dissolved in water, extracted with ethyl acetate. The organic layer was washed with NaHCO3 (sat.), water, and brine, dried over Na2SO4, concentrated in vacuo and purified by column chromatography (15percent ethyl acetate in hexane) to give the title compound as a yellow solid. 1H NMR (300 MHz, CDCl3) delta ppm 4.06 (s, 3H), 7.27-7.40 (m, 6H), 7.45-7.54 (m, 4H), 9.28 (s, 1H).
Step 1: 2-Hydroxy-5,6-diphenylpyrazine. To a stirred suspension of glycinamide hydrochloride (1.1 gm, 10 mmol) in 20 mL MeOH at 0° C. was added 20percent NaOH (10 mL, 50 mmol). A clear solution formed and was treated slowly portionwise with benzil (2.1 gm, 10 mmol) as a solid. The yellow solution was stirred at 0° C. for 2 hours and then neutralized to approximately pH=7 with concentrated HCl. The bright yellow color disappeared and a tan precipitate formed. The material was isolated by filtration with MeOH and triturated with EtOAc to give 2-hydroxy-5,6-diphenylpyrazine (2 gm, 80percent). 1H-NMR (400 MHz, CDCl3) delta8.24 (s, 1H), 7.42-7.31 (m, 4H), 7.39-7.21 (m, 6H).
2,5-bis(4,5-diphenyl-1H-imidazol-2-yl)benzene-1,4-diol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59.6%
With ammonium acetate; acetic acid; for 5h;Reflux;
Synthesis of Example of Compound 1-24; To 30 ml of acetic acid, were added 0.83 g of 2,5-dihydroxy terephthalaldehyde, 2.10 g of benzyl, and 9.25 g of ammonium acetate. Then, the reaction was heated to reflux for about 5 hours, after which the resulted solution was added dropwise to an aqueous solution of a mixture of 10 ml of ammonia water and 200 ml of water. The precipitated crystals were filtered, and the crystals were subjected to suspension washing with ethyl acetate to prepare 1.63 g (59.6%) of 2,5-bis(4,5-diphenyl-1H-imidazole-2-yl)benzene-1,4-diol.
With [(S)-BINAP]PdBr2; hydrogen; In dichloromethane; at 120℃; under 41372.9 Torr; for 48h;Autoclave;
General procedure: From a Schlenk tube under nitrogen atmosphere, a solution of a-diketone (1mmol), aniline (1mmol), [(S)-BINAP]PdBr2] (0.025 mol), in CH2Cl2 (10 ml) was transferred to a 45 ml stainless steel Parr vessel and the vessel was pressurized with 800 psi of hydrogen gas. The reactor was placed in a preheated oil bath at 120 °C with magnetic stirring over different periods of time (24, 48h). The reaction mixture was purified by column chromatography using hexane and methylene chloride as eluents and was analyzed by GC-MS. The formation of intermediates involved in the process was achieved by varying the reaction time (12, 24h), and these intermediates were purified by column chromatography with hexane and ethylacetate as eluents.
With iron oxide; choline chloride; ammonium acetate; urea; at 60℃;Green chemistry;
General procedure: A mixture of benzil (1 mmol), aldehyde (1 mmol) primary amine(1 mmol), ammonium acetate (1 mmol) and eutectic mixture stabilized ferrofluids (0.05 g of Fe3O4 in 1 mL of urea-choline chloride based eutectic mixture) was heated at 60 °C with stirring for 2?6 h.After completion of the reaction, the mixture was cooled to room temperature and water was added and products recrystallized in ethanol. All compounds were characterized on the basis of their spectroscopic data (IR, NMR) and by comparison with those reported in the literature
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux;
A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol.
With indium; acetic acid; In toluene; at 80℃; for 0.666667h;Inert atmosphere;
General procedure: 4.2. General procedure for the indium-mediated reductivecyclization of 2-nitroanilines to prepare quinoxalines A mixture of the 2-nitroaniline derivative (1.0 mmol), dione (1.0or 2.0 mmol), indium (0.574 g, 5.0 mmol), and acetic acid (0.300 g,5 mmol or 0.600 g,10 mmol) or indium chloride (0.221 g,1 mmol or0.265 g,1.2 mmol) in methanol (5 mL) or toluene (5 mL) was stirredat 50 C, 80 C, or reux under a nitrogen atmosphere. After com-pletion of the reaction, the reaction mixture was diluted with ethylacetate (30 mL), ltered through Celite, and the ltrate was pouredinto 10% NaHCO3 (30 mL) and extracted with ethyl acetate(30 mL3). The combined organic extracts were dried over MgSO4,ltered, and concentrated. The residue was eluted with ethyl ace-tate/hexane (v/v10/90) through a silica gel column to give thecorresponding pure quinoxaline. Quinoxaline structures werecharacterized by 1H NMR, 13C NMR, FTIR, and GCeMS, and weremostly known compounds. For unknown compounds, elementalanalysis data were additionally obtained. 4.2.1. 2,3-Dimethylquinoxaline (5).19,31aef Yield 87%. Yellow solid,mp 109e110 C (lit.31f mp 105 C). TLC (10% ethyl acetate/hexane) Rf0.30; 1H NMR (400 MHz, CDCl3) d 7.91 (dd, 2H, J6.3, 3.5 Hz), 7.59(dd, 1H, J6.3, 3.5 Hz), 2.66 (s, 6H); 13C NMR (100 MHz, CDCl3)d 153.4, 141.0, 128.7, 128.2, 23.1; IR (KBr) 3109, 3078, 3030, 2995,2953, 2914, 1490, 1398, 1164 cm1;GCeMS m/z (rel intensity) 158(M, 99), 117 (100), 76 (28), 50 (12).
5,8-dibromo-2,3-diphenylpyrido[3,4-b]pyrazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
66.7%
With acetic acid; at 100℃; for 2.0h;
A mixture of 10 g (37.5 mmol) of <strong>[221241-11-8]2,5-dibromopyridine-3,4-diamine</strong> and 8.66 g (41.2 mmol) of benzil, 200 ml of acetic acid was heated at 100 C. for 2 h. The resulting mixture was allowed to cool to room temperature, and then filtered to get the yellow solid, yield (11 g, 66.7%). 1H NMR (CDCl3, 400 MHz): chemical shift (ppm) 8.50(s, 1H), 7.41-7.51(m, 10H).
1-(4-(1H-imidazol-1-yl)phenyl)-2,4,5-triphenyl-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 mol%) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96% EtOH gave the desired product 3-5.
1-[4-(1H-pyrazol-1-yl)phenyl]-2,4,5-triphenyl-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 molpercent) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 °C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 °C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96percent EtOH gave the desired product 3-5.
4,5-diphenyl-1-[4-(1H-imidazol-1-yl)phenyl]-2-(p-tolyl)-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 mol%) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96% EtOH gave the desired product 3-5.
4,5-diphenyl-1-[4-(1H-pyrazol-1-yl)phenyl]-2-(p-tolyl)-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 molpercent) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 °C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 °C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96percent EtOH gave the desired product 3-5.
4,5-diphenyl-1-[4-(1H-imidazol-1-yl)phenyl]-2-(4-isopropylphenyl)-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
73%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 mol%) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96% EtOH gave the desired product 3-5.
4,5-diphenyl-2-(4-isopropylphenyl)-1-[4-(1H-pyrazol-1-yl)phenyl]-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
62%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 molpercent) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 °C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 °C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96percent EtOH gave the desired product 3-5.
4,5-diphenyl-1-[4-(1H-imidazol-1-yl)phenyl]-2-(4-methoxyphenyl)-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 mol%) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96% EtOH gave the desired product 3-5.
4,5-diphenyl-2-(4-methoxyphenyl)-1-[4-(1H-pyrazol-1-yl)phenyl]-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 molpercent) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 °C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 °C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96percent EtOH gave the desired product 3-5.
2-(4-chlorophenyl)-4,5-diphenyl-1-[4-(1H-imidazol-1-yl)phenyl]-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 mol%) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96% EtOH gave the desired product 3-5.
4,5-diphenyl-1-[4-(1H-imidazol-1-yl)phenyl]-2-(thiophen-2-yl)-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 mol%) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96% EtOH gave the desired product 3-5.
4-{4,5-diphenyl-1-[4-(1H-imidazol-1-yl)phenyl]-1H-imidazol-2-yl}phenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
56%
With bismuth (III) nitrate pentahydrate; ammonium acetate; silica gel; In neat (no solvent); at 110℃; for 24h;
General procedure: A mixture of N-(4-aminophenyl) azoles 2a-d (1 mmol), benzil (1 mmol, 0.21 g), aromatic aldehyde (1 mmol), and ammonium acetate (1 mmol, 0.077 g) was stirred vigorously. Bi(NO3)3*5H2O (0.15 mmol, 0.073 g, 15 mol%) and SiO2 (0.5 g) were mixed effectively and added to the mixed reactants. The resulting mixture was heated at 110 C for 24 h. Acetone (50 mL) was then added and the mixture was stirred at 50 C for 10 min. Filtering the hot mixture and then concentration of the filtrate produced the crude product. Recrystallization of the crude products in 96% EtOH gave the desired product 3-5.
With 10 wtpercent sulfated polyborate; In neat (no solvent); at 100℃; for 0.0833333h;Green chemistry;
General procedure: To a mixture of substituted o-phenylenediamines derivative(2.0 mmol) and 1,2-diketone / alpha-hydroxy ketone (2.0 mmol),was added sulfated polyborate (10 wt%). The reaction mixture was stirred at 100 C in an oil bath. The reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, the mixture was cooled to room temperature and quenched by water. The resultant product was filtered/extracted with EtOAc to get the product. Crude products were either recrystallized from ethanol or purified by column chromatography using silica as the stationary phase and EtOAc: pet. ether as mobile phase. The products obtained were known compounds and were identified by melting point and 1H and 13C NMR spectroscopy. The spectral data were compared with the literature values.
With ammonium acetate; acetic acid; In ethanol;Reflux;
General procedure: Benzil (4.204 g, 20 mmol), 2-bromobenzaldehyde (3.700 g, 20 mmol) and NH4OAc (6.160 g, 80 mmol) were added to a mixture of ethyl alcohol (50.0 mL) and glacial acetic acid (5.0 mL). The mixture was refluxing until all the benzil was consumed which was monitored by TLC. After the completion of the reaction, the desired 2a was obtained as the yellow crystals by a filtration when the mixture was allowed to cool down to room temperature, 92% yield, m.p. 202e203 C (Lit.11 201e202 C). The 4 and 6 were prepared by the same procedure using phenanthrene-9,10-dione and acenaphthylene-1,2-dione as the o-diketones, respectively.
2-(3-chloro-2-nitrophenyl)-4,5-diphenyl-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
With ammonium acetate; acetic acid; at 100℃; for 3.0h;Ionic liquid; Green chemistry;
General procedure: Themixture of aromatic aldehyde 1 (1 mmol), benzil 2 (1 mmol), ammonium acetate (NH4OAc) 3 (5 mmol), acetic acid (3 mL)and ionic liquid [BMIM][BF4] (1 mL) was stirred at 100Cfor 3-4 h. At the end of reaction (monitored by TLC), the mixture was diluted with water (15-20 mL). The crude solid was filtered and washed with water and then recrystallized with 95 % EtOH to provide the pure products 4 (Table-1).
General procedure: The reactions were carried out according to a literature method.2 A solution of i-Pr2NH (1.3 mL, 9.1 mmol) and n-BuLi (4.9 mL, 1.6 M in hexane) in THF (15 mL) was stirred at 0 C for 1.5 h. To this solution was added ketone (5 mmol) in THF (3 mL) at 0 C. After stirring for 1 h, Benzil (6.5 mmol) in THF (5 mL) was added at -78 C dropwise via syringe over 0.5 h. After 12 h, the reaction was quenched with saturated NH4Cl. Products were extracted with EtOAc. Combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give a crude mixture, which was purified by silica gel column chromatography (eluent: EtOAc / hexane = 1/20) to afford 1, 3 as white solid.
General procedure: The reactions were carried out according to a literature method.2 A solution of i-Pr2NH (1.3 mL, 9.1 mmol) and n-BuLi (4.9 mL, 1.6 M in hexane) in THF (15 mL) was stirred at 0 C for 1.5 h. To this solution was added ketone (5 mmol) in THF (3 mL) at 0 C. After stirring for 1 h, Benzil (6.5 mmol) in THF (5 mL) was added at -78 C dropwise via syringe over 0.5 h. After 12 h, the reaction was quenched with saturated NH4Cl. Products were extracted with EtOAc. Combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give a crude mixture, which was purified by silica gel column chromatography (eluent: EtOAc / hexane = 1/20) to afford 1, 3 as white solid.
PCQ was prepared according to the procedure shown in Scheme 1.Benzil (2 mmol, 420 mg) and <strong>[129365-93-1]4,5-diaminophthalonitrile</strong> (2 mmol,316 mg) were dissolved in 10 mL glacial acetic acid in a 25 mL flask.The mixture was stirred and refluxed at 110 C for 3 h to ensure thereaction finish. Then the product was cooled to room temperature to geta yellow precipitate. The precipitate was filtered and washed with 5 mLglacial acetic acid. After being dried under reduced pressure, PCQ wasacquired as light-yellow powder in a yield of 75% (497 mg). 1H NMR(400 MHz, DMSO-d6) delta (ppm): 9.03 (s, 2H), 7.51 (m, 4H), 7.47 (m, 2H),7.40 (m, 4H). 13C NMR (101 MHz, DCCl3) delta (ppm): 57.53, 141.57,137.32, 136.88, 130.41, 129.94, 128.63, 115.08, 114.06. Elementalanalysis, calcd. for PCQ: C 79.50%, H 3.64%, N 16.86%, found: C79.29%, H 3.58%, N 16.55%.
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