* 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] Letters in Drug Design and Discovery, 2013, vol. 10, # 8, p. 783 - 791
2
[ 75-15-0 ]
[ 613-94-5 ]
[ 3004-42-0 ]
Yield
Reaction Conditions
Operation in experiment
96%
With potassium phosphate In water at 20℃; for 2.16667 h; Reflux
A mixture of benzohydrazine (0.41 g, 3 mmol), potassium phosphate (1.02 g, 3 mmol), and carbon disulfide (0.23 g, 3 mmol) in water (15 mL) was stirred at rt for 10 min. After refluxing for an additional 2 h, 1 N HCl was added to pH=7, the solid formed was filtered and dried in vacuum to afford 5-phenyl-1,3,4-oxadiazole-2-thiol 13 (0.51 g, 96percent) as a white solid. Mp: 197-199 °C (lit.22 199-201 °C). 1H NMR (400 MHz, CDCl3) δ 10.52 (br s, 1H), 7.93 (d, J=7.2 Hz, 2H), 7.42-7.65 (m, 3H).
90%
With potassium hydroxide In ethanol for 2 h; Reflux
Take benzoic hydrazide 4.08g (30.00mmol) dissolved in absolute ethanol 50mL,1.85 g (33.00 mmol) of potassium hydroxide was added, and 5.71 g (75.00 mmol) of carbon disulfide was slowly added dropwise with stirring. The mixture was heated to reflux for 2h after the addition was completed. After the reaction was completed, the solvent was distilled off under reduced pressure,The residue dissolved in water, filtered, the filtrate was acidified with dilute hydrochloric acid 5percent to pH 3 ~ 4 precipitated solid,Filtered, washed, dried to give a white solid 4.82g, yield 90percent.
87.2%
With potassium hydroxide In methanol at 20 - 80℃; for 20 h;
In 100 ml round-bottom flask by adding 1.5 g (11.02mmol) [...] and 0.93 g (16.53 mmol) potassium hydroxide, and add 50 ml methanol, dropping 1.00 ml (16.53 mmol) carbon bisulfide, stirring under the room temperature condition to 12h, TLC detection 5 - (4-chlorophenyl) - 1, 3, 4-oxadiazol-2-thiols are all changed into 5 - (4-chlorophenyl) - 1, 3, 4-oxadiazol-2-sulfate potassium salt, then adding 0.62 g (11.02 mmol) potassium hydroxide, the oil bath temperature is 80oC heating to reflux under 8h, TLC detection reaction is over, the solvent is removed by reduced pressure distillation, by adding 30 ml of purified water, using 1M HCl to adjust the pH value 2-3, system precipitating a large amount of white solid, filtering, washing, drying, recrystallized with ethanol, shall be strawcoloured solid 1.71 g, yield 87.2percent, melting point: 219-222oC
86.4%
Stage #1: With potassium hydroxide In ethanol; water for 6 h; Reflux Stage #2: With hydrogenchloride In ethanol; water
General procedure: Hydrazide 3 (0.01 mol) was dissolved in absolute ethanol (10 mL) in a 250 mL round bottom flask. Carbon disulfide (0.03 mol) was then added to the solution followed by the addition of excess potassium hydroxide (0.02 mol) in water (5 mL).This reaction mixture was properly stirred and reflux for 6 h. the mixture was diluted with distilled water (50 mL) and acidified with dilute hydrochloric acid to pH 1–2. It was then filtered, washed with ethanol and distilled water, dried under vacuum, and recrystallized from ethanol to give pure products 4a–4h.
73%
With potassium hydroxide In ethanol at 0℃; for 7 h; Reflux
250mL round bottom flask was added 19. 00g (139. 6mmol) benzoic hydrazide and 100mL of absolute ethanol under ice-cooling (square ° C) with stirring, then added 42. 43g (558. 2mmol) CSjP 7 · 81g (139. 6mmol) K0H, the addition was complete retreatThe ice bath was heated to reflux for 7h. Cooled to room temperature spin off the solvent, the residue after adding an appropriate amount of water dissolved in hydrochloric acid to adjust pH 2~3, stirred 2h, filtration, recrystallized from ethanol to give 18. 16g of white solid, yield 73percent.
73%
Stage #1: With potassium hydroxide In ethanol at 0℃; for 7 h; Reflux Stage #2: With hydrogenchloride In water at 20℃; for 2 h;
250mL round bottom flask was added 19.00g (139.6mmol) of benzoyl hydrazine, and 100mL of absolute ethanol under ice (0oC) with stirring, was added 42.43g (558.2mmol) CS2 and 7.81g (139.6mmol) KOH, feeding finished ice bath was removed, it was heated under reflux for 7 hours. Cooled to room temperature spin off the solvent, the residue was dissolved in water by adding an appropriate amount of hydrochloric acid to adjust the pH to 2-3, stirred for 2 hours, filtration, recrystallized from ethanol to give 18.16g of white solid, yield 73percent.
68.2%
With potassium hydroxide In ethanol for 10 h; Reflux
General procedure: Benzoyl hydrazine (6.81 g, 50 mmol) was added to a solution of KOH (2.8 g, 50 mmol) in 150 mL ethanol, and them carbon disulfide (4.19 g, 55 mmol) was added dropwise. The reaction mixture was refluxed for 10 h before the solvent was evaporated. The residue was neutralized with 10percent aquous HCl. The solid product was collected by filtration and recrystallized from ethanol to give pure white 5-phenyl-[1,3,4]oxadiazole-2-thiol (6.07 g, 68.2percent yield).
40%
at 40 - 70℃; Inert atmosphere
General procedure: To a solution of acid hydrazide in anhydrous 5–15mL of DMF, carbon disulfide (2.5mL/mmol) was added at room temperature and under a nitrogen atmosphere. The reaction mixture was then heated to 40°C for 15min and then to 70°C for 4–8h until the reaction was completed. After completion, the reaction mixture was cooled to room temperature and poured dropwise into ice cold water. The solids formed were separated by filtration, washed with water and dried in vacuo.
Reference:
[1] Tetrahedron, 2012, vol. 68, # 38, p. 7978 - 7983
[2] Patent: CN105837523, 2016, A, . Location in patent: Paragraph 0020; 0024
[3] Patent: , 2016, , . Location in patent: Paragraph 0018
[4] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 481 - 484
[5] Angewandte Chemie - International Edition, 2017, vol. 56, # 7, p. 1885 - 1889[6] Angew. Chem., 2017, vol. 129, # 7, p. 1911 - 1915,5
[7] Asian Journal of Chemistry, 2011, vol. 23, # 5, p. 2007 - 2010
[8] Journal of Medicinal Chemistry, 2016, vol. 59, # 6, p. 2362 - 2380
[9] Organic and Biomolecular Chemistry, 2012, vol. 10, # 9, p. 1785 - 1794
[10] Patent: CN105330651, 2016, A, . Location in patent: Paragraph 0057; 0058; 0059; 0060; 0061
[11] Patent: CN105541748, 2016, A, . Location in patent: Paragraph 0022
[12] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 24, p. 5457 - 5462
[13] Chinese Journal of Chemistry, 2010, vol. 28, # 12, p. 2433 - 2440
[14] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 13, p. 3723 - 3727
[15] European Journal of Medicinal Chemistry, 2010, vol. 45, # 11, p. 4963 - 4967
[16] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 20, p. 5408 - 5419
[17] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 22, p. 2693 - 2698
[18] Journal of the Chinese Chemical Society, 2005, vol. 52, # 3, p. 539 - 544
[19] Phosphorus, Sulfur and Silicon and Related Elements, 2000, vol. 164, p. 67 - 81
[20] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 8, p. 2278 - 2282
[21] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 12, p. 3755 - 3759
[22] Journal of Medicinal Chemistry, 2010, vol. 53, # 20, p. 7392 - 7404
[23] Letters in Organic Chemistry, 2010, vol. 7, # 5, p. 411 - 414
[24] Molecules, 2011, vol. 16, # 2, p. 1297 - 1309
[25] Asian Journal of Chemistry, 2011, vol. 23, # 12, p. 5471 - 5476
[26] European Journal of Medicinal Chemistry, 2012, vol. 47, # 1, p. 473 - 478
[27] Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 4, p. 1036 - 1041
[28] European Journal of Medicinal Chemistry, 2012, vol. 53, p. 308 - 315
[29] Asian Journal of Chemistry, 2012, vol. 24, # 6, p. 2573 - 2578
[30] Phosphorus, Sulfur and Silicon and the Related Elements, 2012, vol. 187, # 11, p. 1401 - 1408
[31] European Journal of Medicinal Chemistry, 2013, vol. 61, p. 26 - 40
[32] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2286 - 2297
[33] Medicinal Chemistry Research, 2013, vol. 22, # 10, p. 4980 - 4991
[34] Chinese Journal of Chemistry, 2013, vol. 31, # 9, p. 1192 - 1198
[35] Medicinal Chemistry Research, 2013, vol. 22, # 11, p. 5344 - 5348
[36] Chemical Biology and Drug Design, 2013, vol. 82, # 5, p. 546 - 556
[37] Patent: US2014/24656, 2014, A1, . Location in patent: Paragraph 0068; 0075
[38] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 10, p. 1318 - 1324
[39] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1423 - 1429
[40] Asian Journal of Chemistry, 2014, vol. 26, # 8, p. 2362 - 2364
[41] Journal of Molecular Structure, 2014, vol. 1074, p. 376 - 383
[42] Journal of Chemical Sciences, 2014, vol. 126, # 3, p. 827 - 835
[43] Pharmaceutical Chemistry Journal, 2015, vol. 49, # 8, p. 523 - 529
[44] Phosphorus, Sulfur and Silicon and the Related Elements, 2015, vol. 190, # 7, p. 1045 - 1055
[45] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 8, p. 1879 - 1888
[46] Chemical Biology and Drug Design, 2017, vol. 90, # 2, p. 236 - 243
[47] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 18, p. 4298 - 4301
[48] Journal of the Chilean Chemical Society, 2017, vol. 62, # 1, p. 3370 - 3375
[49] Russian Journal of Bioorganic Chemistry, 2017, vol. 43, # 3, p. 328 - 339[50] Bioorg. Khim., 2017, vol. 43, # 3, p. 328 - 339,12
[51] Acta Chimica Slovenica, 2017, vol. 64, # 4, p. 895 - 901
3
[ 613-94-5 ]
[ 3004-42-0 ]
Reference:
[1] Phosphorus, Sulfur and Silicon and the Related Elements, 1991, vol. 57, # 1/2, p. 11 - 15
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 1, p. 192 - 194
[3] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 19, p. 5454 - 5465
[4] Comptes Rendus Chimie, 2015, vol. 18, # 12, p. 1320 - 1327
4
[ 137-26-8 ]
[ 613-94-5 ]
[ 3004-42-0 ]
Reference:
[1] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 16, p. 4842 - 4850
5
[ 140-92-1 ]
[ 613-94-5 ]
[ 3004-42-0 ]
Reference:
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 11, p. 1619 - 1622
6
[ 63467-57-2 ]
[ 613-94-5 ]
[ 3004-42-0 ]
Reference:
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 11, p. 1619 - 1622
7
[ 613-94-5 ]
[ 4922-98-9 ]
Reference:
[1] Journal of Medicinal Chemistry, 1996, vol. 39, # 15, p. 3019 - 3029
[2] European Journal of Medicinal Chemistry, 2013, vol. 67, p. 325 - 334
[3] European Journal of Medicinal Chemistry, 2016, vol. 113, p. 11 - 27
[4] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 774 - 789
4-(2-(2-tert-Butylphenoxy)pyridin-3-yl)-1-phenylsemicarbazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With 1,1'-carbonyldiimidazole; In tetrahydrofuran; at 20℃; for 72h;
A mixture of <strong>[861673-68-9]2-(2-tert-butylphenoxy)-3-aminopyridine</strong> (Intermediate 1) (358 mg, 1.48 mmol), 1,1-carbonylimidazole (239 mg, 1.48 mmol) and benzoic hydrazide (200 mg, 1.48 mmol) in THF (10 mL) was stirred at room temperature for 72 h. Saturated ammonium chloride (15 mL) was added and the mixture was extracted with ethyl acetate (3×25 mL). The combined organic layers were dried (anhydrous sodium sulfate), filtered and evaporated to yield an oily residue which was purified by reverse phase preparative HPLC to afford Example 203a (75 mg). (M+H)+=405.
1-trichloroacetimidoyl-2-benzoylhydrazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
EXAMPLE 1 Preparation of 1-Trichloroacetimidoyl-2-Benzoylhydrazine A mixture of 9.1 g (0.07 mole) benzoylhydrazine and 20 ml (28.5 g, 0.16 mole) <strong>[2533-69-9]methyl 2,2,2-trichloroacetimidate</strong> was stirred 16 hours at room temperature. The solid that was left was washed with petroleum ether and dried to give 18.6 g (100% yield) of product (mp 170-172 C.). A sample recrystallized from ethanol had mp 178-181 C. The structure was confirmed via infrared and elemental analysis.
1-benzoyl-4-(2-phenoxypyridin-3-yl)semicarbazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
A mixture of <strong>[861673-68-9]2-(2-tert-butylphenoxy)pyridin-3-amine</strong> (1a) (212 mg, 0.88 mmol) and 1,1-carbonylimidazole (142 mg, 0.88 mmol) in THF (2.5 mL) was stirred at rt for 2 h. Benzoyl hydrazide (120 mg, 0.88 mmol) was then added and the mixture was stirred at rt for 16 h. A saturated solution of ammonium chloride (10 mL) and ethyl acetate (20 mL) was then added. The separated aqueous solution was extracted with ethyl acetate (3×15 mL) and the combined organic layers were washed with brine, dried (anh. magnesium sulfate), filtered and evaporated. Purification by Prep. HPLC (C18 20 mm×100 mm, 20-100% solvent B, 10 min. gradient, 7 min. 20 ml/min: solvent A=10% MeOH/Water+0.05% ammonium acetate, solvent B=90% MeOH[Water+0.05% ammonium acetate) provided Example 60 (90 mg, 0.24 mmol). (M+H)+=405.
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; for 36.0h;
Synthesis 523-Methyl-8-(5-phenyl-1 ,3,4-oxadiazol-2-yl)imidazo[5,1-d][1 ,2,3,5]tetrazin-4(3H)-one(WW-041)3-Methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1 ,2,3,5]tetrazine-8-carboxylic acid (0.26 mmol), EDCI (0.26 mmol) and benzoyl hydrazide (0.26 mmol) were stirred in MeCN (1.5 mL) for 36 hours. The yellow precipitate which formed was filtered, washed with diethyl ether and dried to give N'-benzoyl-3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1 ,2,3,5]tetrazine-8- carbohydrazide (72%). deltaH (DMSO-d6): 10.54 (1H, s), 10.42 (1 H, s), 8.91 (1H, s), 7.93 (2H, dd, J = 5.2 & 7.2), 7.59 (3H, m), 3.89 (3H, s).N'-Benzoyl-3-methyl-4-oxo-3,4-dihydroimidazo[5, 1 -d][1 ,2,3,5]tetrazine-8-carbohydrazide (0.03 mmol), carbon tetrabromide (0.06 mmol) and triphenylphosphine (0.06 mmol) were stirred in DCM (0.5 mL) for 3 hours. The crude reaction mixture was purified by column chromatography, eluting with 10% MeCN/DCM, to give the title compound. deltaH (DMSO-Cf6) 9.06 (1 H, s), 8.11 (2H, m), 7.67 (3H, m), 3.93 (3H, s).
N’-((5-nitrofuran-2-yl)methylene)benzohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
91%
With sulfuric acid; acetic acid; In methanol; water; for 1h;Reflux;
General procedure: Compounds of series I were synthesized by refluxing <strong>[92-55-7]5-nitro-2-furaldehyde diacetate</strong> 98% (5 mmol) and benzhydrazides (3) (5 mmol) in water, sulphuric acid, acetic acid, and methanol (8:7:8:20 v/v) for 1 h. After cooling, the mixture was poured into cold water to precipitate the azomethine derivatives 20(see structural elucidation of the compounds of series I in Supplementary data, p. S2).
A 22 L three-neck flask was charged with (lr,4r)-4-((tert- butoxycarbonyl)amino)cyclohexanecarboxylic acid (commercially available from Albany Molecular Research, Inc., Albany, NY) (227 g, 0.933 mol), benzohydrazide (127 g, 0.933 mol) and ACN (9 L). DIEA (488 mL, 2.799 mol) was added to the solution and the resulting mixture was stirred at room temperature for 10 minutes. HATU (390 g, 1.026 mol) was added in portions over 10 minutes and the resulting yellow mixture was stirred at room temperature for 23 hours. DIEA (325 mL, 1.866 mol) was added, followed by p-TsCl (534 g, 2.799 mol) over 5 minutes. The resulting orange suspension was then stirred at room temperature under nitrogen for 23 hours and the mixture turned dark brown. To the mixture was added DCM (2.5 L), followed by 15percent ammonium hydroxide (2.5 L) and the mixture was stirred at room temperature for 1 hour. After separation, the aqueous layer was extracted with DCM (2.5 L) and the combined organic layers were dried over MgSO/t, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (eluting with hexanes/EtOAc = 4: 1 to 2: 1) to yield 575 g of tert-butyl ((lr,4r)-4-(5- phenyl-l,3,4-oxadiazol-2-yl)cyclohexyl)carbamate which was still contaminated with / toluene sulfonamide (as evident by lH NMR) and was used in the next step without further purification.
General procedure: The Compound I (0.79 mmol)was dissolved in 10 mL of absolute ethanol. Then the mixture of R2-CHO (0.66 mmol), 10 mL acetic acid and 3 mL absolute ethanol was added dropwise at 70 °C. The mixture was refluxed for 5 h. The solvent was evaporated. The crude product was purified by flash chromatography (neutral Al2O3).
General procedure: 5,5'-Bis-vanillin (1) (0.66 mmol) was suspended in absolute ethanol (30 ml) and semicarbazide (1.32 mmol) was added to the suspension. The reaction mixture was refluxed for 24 h. At the beginning of the heating all product is dissolved and over time it begins to appear a new precipitate. The solid was filtered and dried to give a pure solid.
(E)-N'-[(4-phenyl-1H-imidazol-2-yl)methylene]benzohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
In ethanol; for 1h;Reflux;
General procedure: To a stirred solution of compound 3 (100mg, 0.40 mmol) in ethanol was added corresponding benzohydrazides (4a-m) (1.0 mmol) and refluxed for 1 h. The reaction mass was washed with pet ether, filtered and dried undervacuum to obtain the pure hydrazone compounds. Yields ofthe products varied between 78 and 88 %.
2-(2-bromoethyl)-5-phenyl-1,3,4-oxadiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With trichlorophosphate; In toluene; at 100℃; for 2h;
A mixture of benzoylhydrazine 23 (0.68g, 5mmol), 3-<strong>[590-92-1]bromopropionic acid</strong> (1.2g, 7.5mmol), POCl3 (4mL) in toluene (20mL) was stirred at 100C for 2h. After cooling to room temperature, the mixture was poured into ice water slowly, and extracted with ethyl acetate (20mL×3). The organic layer was combined, dried over Na2SO4, and concentrated to afford crude 2-(2-bromoethyl)-5-phenyl-1,3,4- oxadiazole 19o as a yellow solid in 41% of yield. This crude product was used without purification. (0056) Following the same procedure for the synthesis of 17a, target compound 17o was obtained using crude 2-(2-bromoethyl)-5-phenyl-1,3,4-oxadiazole 19o as halide. Yield 62%. White solid. MP: 134-136C. 1H NMR (400MHz, CDCl3): delta 3.35-3.38 (t, J=6.8Hz, 2H), 3.76-3.79 (t, J=6.8Hz, 2H), 4.95 (d, J=5.2Hz, 2H), 7.19-7.21 (m, 1H), 7.45-7.51 (m, 3H), 7.68-7.70 (m, 1H), 7.98-8.00 (m, 2H), 8.39-8.49 (m, 2H), 9.11 (bs, 1H). 13C NMR (100MHz, CDCl3): delta=26.08, 31.43, 48.18, 123.62, 126.85, 129.04, 131.75, 132.45, 136.24, 148.85, 149.40, 165.02, 165.07, 197.39. Anal. Cald for C17H16N4OS2: C, 57.28; H, 4.52; N, 15.72; Found: C, 57.32; H, 4.64; N, 15.66.
With potassium carbonate; In N,N-dimethyl-formamide; at 25℃; for 24h;Sealed tube; Irradiation;
General procedure: A sealed tube equipped with a magnetic stir bar was charged with acylhydrazine 1 (0.5 mmol), alpha-keto acid 2 (0.5 mmol), K2CO3 (1 mmol), PANI-g-C3N4-TiO2 (40 mg) and DMF (5.0 mL). The mixture was then irradiated with a 14 W CFL and stirred at room temperature (25 C) for 24 h. The distance of the reaction vial from the light is about 5 centimeters. After reaction, the mixture was diluted with EtOAc (10 mL) and H2O (5 mL), and the solid catalyst was recovered by centrifugation. The aqueous phase was extracted with EtOAc (5 mL × 3). The collected organic extracts were dried on Na2SO4, filtered and evaporated to dryness. The crude was purified by flash chromatography on silica gel using a mixture of PE/EA (20:1) to give the pure product 3.
77%
With tert.-butylhydroperoxide; sodium carbonate; potassium iodide; In 1,4-dioxane; at 120℃; for 5h;Sealed tube;
General procedure: In a 35 mL sealed tube, a solution of 3 mL of 1,4-dioxane, acyhydrazines 1 (0.5mmol), alpha-ketoacids 2 (0.5 mmol) , Na2CO3 (0.6 mmol), KI (0.05 mmol) and TBHP (2.0 mmol) was sequentially added. The reaction mixture was stirred at 120 C for 5 h and then cooled to room temperature. Then, the mixture extracted with ethyl acetate (2 × 10 mL), and the organic layer was combined and dried with anhydrous Na2SO4. After removal of the solvent under reduced pressure, the residue was separated by flash column chromatography to afford the pure product 3 (PE:EA = 20:1).
N-[4-(3-phenyl-4H-1,2,4-triazol-4-yl)phenylsulfonyl]acetamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
With acetic acid; In acetonitrile; for 9h;Reflux;
General procedure: A mixture of benzoylhydrazine (1.22 g, 0.01mol), dimethylformamide-dimethylacetal (1.91 g,0.01 mol)) and sulfa-drugs (0.012 mol) in dry acetonitrile(15 mL) containing acetic acid (3 mL) was refluxed for 9 h., then left to cool. The solid product formed was collected by filtration and recrystallized from dioxane to give compounds 1-13, respectively.
N’-((2,4-diaminopyrimidine-5-yl)methylene)benzohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
With acetic acid; In ethanol; for 3h;
General procedure: Appropriate substituted benzoyl hydrazine 4 (1 equiv) was added to a solution of intermediate 2 (1mmol) in ethanol (10mL). The reaction mixture was stirred for 3h at reflux under the condition of the presence of acetic acid as catalyzer, then poured into cold water and the resulting solid was collected by filtrated, washed with EtOH (10mL), and dried in the atmospheric pressure to give the desired title compounds A, B, and C.
79%
With trifluoroacetic acid; In ethanol;Heating;
1mmol <strong>[20781-06-0]2,4-diamino-5-pyrimidinecarbaldehyde</strong> with1.1mmol benzoyl hydrazide is dissolved in 25ml ethanol solvent,Add 0.15 mmol of trifluoroacetic acid,Heat and stir the reaction for 6-8h,TLC monitors the progress of the reaction,Add 50ml of water after the reaction is completed.Stirring solids precipitated,Filtering,Drying gave a yellow solid.Yield 79%, m.p. 250-252 C;
2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-5-phenyl-1,3,4-oxadiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With trichlorophosphate; for 10h;Heating;
step 3: Add 0.30 g of 3-chloro-5-(trifluoromethyl)pyridinecarboxylic acid to a three-necked flask.0.18g benzoyl hydrazide, 3ml phosphorus oxychloride, heated and stirred,After 10 hours of reaction, pour the liquid into a beaker containing ice water.Add Na2CO3 to adjust pH = 9-10, suction filtration, drying, and column chromatography to obtain the target compound.
N-(2-(4-chlorophenyl)-4-methylene-5-oxo-2-(trifluoromethyl)pyrrolidin-1-yl)benzamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
General procedure: Trifluoromethyl ketones (1; 0.30 mmol, 1 equiv), acylhydrazines (2; 0.45 mmol, 1.5 equiv) and TsOH (20 mol%) were added to a dried round-bottom flask (50 mL) fitted with a magnetic bar. 1,4-Dioxane 4 mL) was then added and the mixture was stirred and heated to reflux. After the formation of acylhydrazones (monitored by TLC), tin powder (1.35 mmol, 4.5 equiv) and ethyl 2-(bromomethyl)acrylate (3; 1.20 mmol, 4 equiv) were added to the flask. When acylhydrazones had essentially disappeared (monitored by TLC), the reaction mixture was cooled to r.t., then 1,4-dioxane was removed under vacuum. Saturated NH4Cl solution (10 mL) was added and the mixture was stirred for 10 min. The mixture was extracted with EtOAc (3 × 10 mL) and the combined organic phases were dried (MgSO4) and concentrated. Purification of the residue by silica gel column chromatography (petroleum ether-EtOAc, 4:1) furnished the pure products 4.
2-(6-methoxyquinolin-2-yl)-5-phenyl-1,3,4-oxadiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
The specific steps are as follows: adding 0.6 mmol of <strong>[1078-28-0]6-methoxy-2-methylquinoline</strong>, 0.9 mmol of elemental iodine, and 2 mL of dimethyl sulfoxide to a 15 mL pressure tube, and magnetically stirring the reaction at 110 C for 4 hours. After cooling, 0.5 mmol of benzoyl hydrazide and 3 mmol of potassium carbonate were added, and magnetic stirring was carried out at 110 C for 6 hours. After the reaction was completed, the reaction solution was extracted, and the organic layer was washed and dried.Dry and vacuum distillation to remove the solvent to obtain the crude product. The crude product is purified by column with petroleum ether/ethyl acetate=5:1 (V/V) as the eluent to obtain the desired product. The product is yellow solid. The rate is 71%.
With potassium carbonate; dimethyl sulfate; In water; at 50℃; for 16h;Green chemistry;
General procedure: A suspension of thiourea (1) (0.076 g, 1 mmol), hydrazides 3a-j (1 mmol), dimethyl sulfate (2) (0.063 g, 0.5 mmol) and potassium carbonate (0.069 g, 0.5 mmol) in 4 mL water was heated at 50 C for 15-20 h. The reaction progress was checked with TLC. The mixture was cooled in an ice bath in order to increase in total precipitation. The solid was fltered of, washed with cold water and ethanol, and dried in an oven at 60 C without need for further purifcation. 3(5)-Phenyl-1H-1,2,4-triazol-5(3)-amine (4a): White solid; FTIR (KBr) nu: 3415, 2981, 2364, 1643, 1551, 1364, 1290, 1142, 694 cm-1; 1H NMR (400 MHz, DMSO-d6) delta: 11.86 (1H, br, NH), 7.91-7.78 (2H, m, H-2,6), 7.53-7.25 (3H, m, H-3,4,5), 6.80 (2H, br, NH2) ppm; 13C NMR (100 MHz, DMSO-d6) delta: 161.6, 163.6 (C-3, C-5), 132.2 (C-1), 128.4 (C-3,5), 128.0 (C-4), 127.1 (C-2,6) ppm. Anal. Calcd for C8H8N4: C 59.99, H 5.03, N 34.98; found: C 60.02, H 5.04, N 34.94.
benzoic acid [1‑(4‑methyl‑3‑nitrophenyl)ethylidene]hydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
97%
With aluminium(III) chloride hexahydrate; In water; at 60℃; for 1.5h;Green chemistry;
General procedure: acylhydrazines (1 mmol), aromatic ketones (1 mmol), and AlCl3·6H2O (0.1 mmol) were first charged to a round-bottom flask. 10 cm3 water was also added to the flask. Then the reaction mixture was heated to 60 C and stirred. TLC was used to monitor reaction progress. After the reaction was completed, solids were collected by filtration; the filtrate was washed by water. The product was drained by vacuum pump to afford desired compound.
benzoic acid [1‑(3,4‑difluorophenyl)ethylidene]hydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With aluminium(III) chloride hexahydrate; In water; at 60℃; for 1.5h;Green chemistry;
General procedure: acylhydrazines (1 mmol), aromatic ketones (1 mmol), and AlCl3·6H2O (0.1 mmol) were first charged to a round-bottom flask. 10 cm3 water was also added to the flask. Then the reaction mixture was heated to 60 C and stirred. TLC was used to monitor reaction progress. After the reaction was completed, solids were collected by filtration; the filtrate was washed by water. The product was drained by vacuum pump to afford desired compound.