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Structure of 5281-18-5 * Storage: {[proInfo.prStorage]}
* 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.
With hydrazine hydrate In neat (no solvent) for 6 h; Reflux
General procedure: Amixture ofDHPMs a–h(0.01mol) and excess hydrazine hydrate (5 mL) was heatedunder reflux for 6 h. The reaction mixture was allowed tocool and poured on crushed ice.The obtained solid producta–d was filtered, crystallized from ethanol, and finallydried.The evaporation of the filtrate gave solid residue whichupon fractional crystallization from water gave the pyrazole and urea (a)/thiourea (b), respectively. 2.4.1. 3-Methyl-1H-pyrazol-5-ol (13). Yield: 42–55percent (for a–h); m.p. 221–223 °C (Lit. [49] m.p. 220–222 °C); 1H-NMR(DMSO-6) δ (ppm): 2.47 (s, 3H, -CH3), 6.83 (s, 1H, Ar-H),10.07 (s, 1H, OH), 12.10 (s, 1H,NH).
Reference：
[1] Journal of Chemistry, 2018, vol. 2018,
2
[ 123237-03-6 ]
[ 5281-18-5 ]
[ 17356-08-0 ]
[ 57-13-6 ]
[ 132712-71-1 ]
Yield
Reaction Conditions
Operation in experiment
55%
With hydrazine hydrate In neat (no solvent) for 6 h; Reflux
General procedure: Amixture ofDHPMs a–h(0.01mol) and excess hydrazine hydrate (5 mL) was heatedunder reflux for 6 h. The reaction mixture was allowed tocool and poured on crushed ice.The obtained solid producta–d was filtered, crystallized from ethanol, and finallydried.The evaporation of the filtrate gave solid residue whichupon fractional crystallization from water gave the pyrazole and urea (a)/thiourea (b), respectively. 2.4.1. 3-Methyl-1H-pyrazol-5-ol (13). Yield: 42–55percent (for a–h); m.p. 221–223 °C (Lit. [49] m.p. 220–222 °C); 1H-NMR(DMSO-6) δ (ppm): 2.47 (s, 3H, -CH3), 6.83 (s, 1H, Ar-H),10.07 (s, 1H, OH), 12.10 (s, 1H,NH).
Reference：
[1] Journal of Chemistry, 2018, vol. 2018,
3
[ 100-52-7 ]
[ 5281-18-5 ]
Yield
Reaction Conditions
Operation in experiment
100%
With hydrazine hydrate In ethanol at 20℃; for 100 h; Inert atmosphere
To a solution of hydrazine hydrate (2.5 mL, 30 mmol) in EtOH (10 mL) benzaldehyde (1.04 mL, 10 mmol) was added dropwise under nitrogen over 10 min. The resulting solution was stirred at RT for 1.5 h. After this time, water was added and ethanol was evaporated under vacuum. The aqueous phase was extracted with DCM (x 4). Combined organics were dried and concentrated to obtain (phenylmethylidene)hydrazine (p2, 1.2 g, y= quant.) as yellow oil MS (/T7/z): 121.1 [MH]+
Reference：
[1] Patent: WO2016/67043, 2016, A1, . Location in patent: Page/Page column 88
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[7] Organometallics, 2015, vol. 34, # 13, p. 3264 - 3271
[8] Chemistry - A European Journal, 2015, vol. 21, # 40, p. 13996 - 14001
[9] Journal fuer Praktische Chemie (Leipzig), 1891, vol. <2> 44, p. 540
[10] Chemische Berichte, 1943, vol. 76, p. 1252,1254
[11] Anales de la Real Sociedad Espanola de Fisica y Quimica, 1918, vol. 16, p. 713
[12] Journal of Organic Chemistry, 1961, vol. 26, p. 1847 - 1849
[13] Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 1845 - 1848
[14] Synlett, 1999, # 10, p. 1573 - 1574
[15] Tetrahedron, 2001, vol. 57, # 35, p. 7519 - 7527
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[19] Synthesis, 2005, # 4, p. 605 - 609
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[21] Chemical Research in Toxicology, 2010, vol. 23, # 1, p. 48 - 54
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[29] Organic Letters, 2014, vol. 16, # 8, p. 2232 - 2235
[30] Organic Letters, 2014, vol. 16, # 13, p. 3588 - 3591
[31] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 17, p. 4176 - 4180
[32] Tetrahedron Letters, 2014, vol. 55, # 48, p. 6601 - 6604
[33] Patent: US9115171, 2015, B2, . Location in patent: Page/Page column 102-103
[34] Chemical Communications, 2016, vol. 52, # 47, p. 7501 - 7504
[35] Journal of Medicinal Chemistry, 2016, vol. 59, # 18, p. 8549 - 8576
[36] Nature Chemistry, 2017, vol. 9, # 4, p. 374 - 378
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[44] Organic and Biomolecular Chemistry, 2017, vol. 15, # 45, p. 9643 - 9652
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[46] Medicinal Chemistry, 2018, vol. 14, # 2, p. 181 - 199
[47] Organic Letters, 2018, vol. 20, # 13, p. 3801 - 3805
[48] European Journal of Organic Chemistry, 2018, vol. 2018, # 27, p. 3816 - 3825
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With hydrazine hydrate In neat (no solvent) for 6 h; Reflux
General procedure: Amixture ofDHPMs a–h(0.01mol) and excess hydrazine hydrate (5 mL) was heatedunder reflux for 6 h. The reaction mixture was allowed tocool and poured on crushed ice.The obtained solid producta–d was filtered, crystallized from ethanol, and finallydried.The evaporation of the filtrate gave solid residue whichupon fractional crystallization from water gave the pyrazole and urea (a)/thiourea (b), respectively. 2.4.1. 3-Methyl-1H-pyrazol-5-ol (13). Yield: 42–55percent (for a–h); m.p. 221–223 °C (Lit. [49] m.p. 220–222 °C); 1H-NMR(DMSO-6) δ (ppm): 2.47 (s, 3H, -CH3), 6.83 (s, 1H, Ar-H),10.07 (s, 1H, OH), 12.10 (s, 1H,NH).
Reference：
[1] Journal of Chemistry, 2018, vol. 2018,
6
[ 123237-03-6 ]
[ 5281-18-5 ]
[ 17356-08-0 ]
[ 57-13-6 ]
[ 132712-71-1 ]
Yield
Reaction Conditions
Operation in experiment
55%
With hydrazine hydrate In neat (no solvent) for 6 h; Reflux
General procedure: Amixture ofDHPMs a–h(0.01mol) and excess hydrazine hydrate (5 mL) was heatedunder reflux for 6 h. The reaction mixture was allowed tocool and poured on crushed ice.The obtained solid producta–d was filtered, crystallized from ethanol, and finallydried.The evaporation of the filtrate gave solid residue whichupon fractional crystallization from water gave the pyrazole and urea (a)/thiourea (b), respectively. 2.4.1. 3-Methyl-1H-pyrazol-5-ol (13). Yield: 42–55percent (for a–h); m.p. 221–223 °C (Lit. [49] m.p. 220–222 °C); 1H-NMR(DMSO-6) δ (ppm): 2.47 (s, 3H, -CH3), 6.83 (s, 1H, Ar-H),10.07 (s, 1H, OH), 12.10 (s, 1H,NH).
Reference：
[1] Journal of Chemistry, 2018, vol. 2018,
7
[ 1075-70-3 ]
[ 5281-18-5 ]
Reference：
[1] European Journal of Medicinal Chemistry, 1985, vol. 20, # 4, p. 363 - 370
[2] Journal of Organic Chemistry, 1966, vol. 31, p. 677 - 681
8
[ 70509-12-5 ]
[ 5281-18-5 ]
Reference：
[1] J. Gen. Chem. USSR (Engl. Transl.), 1990, vol. 60, # 12.1, p. 2434 - 2438[2] Zhurnal Obshchei Khimii, 1990, vol. 60, # 12, p. 2716 - 2721
9
[ 100-52-7 ]
[ 5281-18-5 ]
[ 28867-76-7 ]
Reference：
[1] Liebigs Annalen der Chemie, 1982, # 5, p. 994 - 1000
With hydrazine hydrate; In ethanol; at 20℃; for 100.0h;Inert atmosphere;
To a solution of hydrazine hydrate (2.5 mL, 30 mmol) in EtOH (10 mL) benzaldehyde (1.04 mL, 10 mmol) was added dropwise under nitrogen over 10 min. The resulting solution was stirred at RT for 1.5 h. After this time, water was added and ethanol was evaporated under vacuum. The aqueous phase was extracted with DCM (x 4). Combined organics were dried and concentrated to obtain (phenylmethylidene)hydrazine (p2, 1.2 g, y= quant.) as yellow oil MS (/T7/z): 121.1 [MH]+
With hydrazine hydrate; In ethanol; at 0℃; for 1.5h;
To solution of hydrazine hydrate (9.7 ml, 200 mmol) in absolute EtOH (350 ml) at 0 C, benzaldehyde (21.2 ml, 200 mmol) was added. After 1.5 h, ethoxymethylenemalononitrile (24.4 g, 200 mmol) was added and the resulting solution was stirred for 1 h at room temperature. After cooling overnight, the yellowish precipitate was collected, washed with cold EtOH and recrystallized from CHCl3.CommentYield 82% 1H NMR (300 MHz, DMSO-d6): delta 7.43-7.52 (3H, m, aromatic HA+B), 7.64-7.73 (2H, m, aromatic HB), 7.76-7.84 (2H, m, aromatic HA), 7.86 (1H, s, CHA), 8.20 (1H, s, CHA), 8.43 (1H, s, CHB), 8.45 (1H, s, CHB), 12.45 (1H, br s, NHA+B).
With hydrazine hydrate; In ethanol; at 0℃;
To a stirred solution of EtOH (1.5 mL) in a vial equipped with a magnetic stirrer at 0 C, was added hydrazine hydrate (56 muL, 1.8 mmol). To this reaction mixture, dropwise addition of benzaldehyde (61 muL, 0.6 mmol) was added. The reaction progress was tracked by TLC, [(2:1 Hexane:EtOAc), Rf (benzaldehyde): about 0.7 and Rf (benzaldehyde hydrazone): about 0.6] which indicated complete reaction in about 15 min. The reaction mixture was quenched in H2O (5 mL) and the desired benzaldehyde hydrazone was extracted with DCM (3 x 5 mL). The organic phase was dried with anhydrous MgSO4 orNa2SO4, concentrated to yield the crude product (70 mg, 98%) that was employed without further purification. Benzaldehyde hydrazone (70 mg, 0.6 mmol, 3 equiv.) was dissolved in DCM (1 mL) and added dropwise over 15 min to a solution of p-nitrophenyl chloroformate (123 mg, 0.61 mmol, 3.2 equiv.) in DCM (1 mL) at 0 C. The reaction mixture was warmed to room temperature (22 C) and stirred for an additional 1.5 h under nitrogen. Complete conversion of the starting material to the activated carbazate intermediate (2) was confirmed by TLC [(2:1 Hexane:EtOAc), Rf: 0.75]. DIEA (210 muL, 1.2 mmol, 6 equiv.) was added to neutralize the reaction mixture (20 min at 0 C) and the suspension was added to the resin for the coupling reaction. This reaction was mixed on an automated shaker for 16 h at room temperature. The next day, the resin was filtered and washed under vacuum with DMF (3x 10 mL), MeOH (3 x 10 mL), THF (3 x 10 mL), and DCM (3 x 10 mL). The reaction conversion was monitored by analyzing a small sample of resin (~3 mg) by LCMS following peptide cleavage and deprotection [1 mL, TFA/TES/H2O (95:2.5:2.5, v/v/v)] from the solid support.
With hydrazine hydrate; In ethanol; at 20℃; for 0.08333330000000001h;
General procedure: In a typical procedure, aldehyde (1 mmol) in 5 mL ethanol was mixed with hydrazine hydrate (1 mmol), the mixture was stirred for 5 min at room temperature furnished the corresponding hydrazone. To the resultant mixture,TMSNCS (1 mmol) was added, followed by 20 mol % of sulfamic acid and allowed to stir at reflux condition for a period mentioned in Table 2. The progress of the reaction was monitored by TLC. After completion of reaction,the mixture was allowed to cool at room temperature and ice cold water was added to it. The precipitated product was isolated by simple filtration and washed with ethanol. The products were characterized by spectral analysis viz. IR, 1H and 13C NMR as well as MS.
With hydrazine hydrate; In ethanol; at 0℃; for 0.25h;
To a stirred solution of EtOH (1.5 mL) and hydrazine hydrate (60 muL, 1.8 mmol) at 0 C., benzaldehyde (60 muL, 0.6 mmol) was added dropwise to generate the phenyl hydrazone. The reaction was stirred to completion which was usually after 15 min as indicated by TLC, [(2:1 Hex:EtOAc), Rf (benzaldehyde): 0.7 and Rf (benzaldehyde hydrazone): 0.6], and poured directly into H2O (5 mL) and extracted in DCM (3×5 mL). The organic phase was dried with MgSO4 and concentrated in-vacuo to yield the benzaldehyde hydrazone as a yellow-tinged oil that was employed directly without further purification.
With hydrazine hydrate; In tetrahydrofuran; at 20℃; for 0.5h;
General procedure: A mixture of carbonyls (0.48 mmol, 1.2 equiv.) and hydrazine monohydrate (26 mul, 0.52 mmol, 64-65 wt%, 1.3 equiv.) in THF (0.2 ml) solution was stirred for 30 min at room temperature. Before injection of this hydrazone solution A into the reaction mixture, a small amount of anhydrous Na2SO4 was added to it.
With hydrazine; In ethanol; for 3.0h;Reflux;
General procedure: To a solution of hydrazine hydrate (1 mL) in ethanol (1mL) was added the appropriate benzaldehyde (1 mmol). The reaction mixture was refluxed for three hours and subsequently cooled to room temperature. The precipitate was isolated by filtration and recrystallized with ethanol. No further purification was required.
With hydrazine hydrate; In ethanol; at 20℃; for 6.0h;
General procedure: To the solution of aryl aldehyde 1 (5.0 mmol, 1 Eq.) in Ethanol (10 vol), Hydrazinehydrate (5.0 mmol, 1 Eq.) was added and stirred at room temperature for 6 h. Then the reaction was monitored by TLC, after the completion of the reaction, the reaction mixture was allowed to cool at room temperature, which was diluted with water and the aqueous layer was extracted with ethyl acetate (25mL 3), dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure to get benzylidenehydrazine which was then taken to the next step without any purification.
1-[(2-benzylidenehydrazinyl)(phenyl)methyl]-1H-imidazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With dichloro(1,10-phenanthroline) copper(II); In ethanol;
General procedure: To a mixture of imidazole (0.1 mol), (furan-2-ylmethylidene)hydrazine (0.1 mol), and 4-subsituted benzaldehyde (0.1 mol) in 30 cm3 of EtOH was added Cu(Phen)Cl2(10 mol %) at room temperature. The reaction mixture was refluxed for 5 h. The reaction was checked by TLC, and then the solvent was removed under reduced pressure. The final product was purified by flash column chromatography on silica gel using n-hexane/EtOAc.
5-[(2-benzylidenehydrazinyl)(1H-imidazol-1-yl)methyl]thiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With dichloro(1,10-phenanthroline) copper(II); In ethanol;
General procedure: To a mixture of imidazole (0.1 mol), (furan-2-ylmethylidene)hydrazine (0.1 mol), and 4-subsituted benzaldehyde (0.1 mol) in 30 cm3 of EtOH was added Cu(Phen)Cl2(10 mol %) at room temperature. The reaction mixture was refluxed for 5 h. The reaction was checked by TLC, and then the solvent was removed under reduced pressure. The final product was purified by flash column chromatography on silica gel using n-hexane/EtOAc.
With potassium phosphate; Fe(1,2-bis(dimethylphosphino)ethane)2Cl2; cesium fluoride In tetrahydrofuran at 20℃; for 24h; Glovebox; Inert atmosphere;
With potassium phosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1,2-bis(dimethylphosphanyl)ethane; cesium fluoride In tetrahydrofuran at 45℃; for 3h; Inert atmosphere;
General procedure
General procedure: A flame-dried V-shape microwave reaction vial (10 cm3) equipped with a magnetic stir bar was charged with [Ru(p-cymene)Cl2]2 (1.8 mg, 0.003 mmol, 0.75 mol%) and K3PO4 (21.2 mg, 0.1 mmol, 25 mol%). The reaction vial was transferred to the glovebox and charged with dmpe (1.0 μl, 0.006 mmol, 1.5 mol%) and CsF (30 mg, 0.20 mmol, 50 mol%) before being sealed with a rubber septum. The reaction vial was moved out of the glovebox and sequentially charged with ketones or aldehydes (0.4 mmol, 1.0 equiv.) and hydrazone solution (250 μl). The reaction mixture was heated to 45 °C in an oil bath. Following stirring for 3 h, the reaction mixture was filtered through a plug of silica gel with EtOAc (2 ml) as eluent, concentrated, and purified by flash chromatography (hexane/ethyl acetate 90:10 as eluent) to give the corresponding alcohols.
With potassium phosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1,2-bis(dimethylphosphanyl)ethane; cesium fluoride In tetrahydrofuran at 45℃; for 3h; Inert atmosphere;
General procedure
General procedure: A flame-dried V-shape microwave reaction vial (10 cm3) equipped with a magnetic stir bar was charged with [Ru(p-cymene)Cl2]2 (1.8 mg, 0.003 mmol, 0.75 mol%) and K3PO4 (21.2 mg, 0.1 mmol, 25 mol%). The reaction vial was transferred to the glovebox and charged with dmpe (1.0 μl, 0.006 mmol, 1.5 mol%) and CsF (30 mg, 0.20 mmol, 50 mol%) before being sealed with a rubber septum. The reaction vial was moved out of the glovebox and sequentially charged with ketones or aldehydes (0.4 mmol, 1.0 equiv.) and hydrazone solution (250 μl). The reaction mixture was heated to 45 °C in an oil bath. Following stirring for 3 h, the reaction mixture was filtered through a plug of silica gel with EtOAc (2 ml) as eluent, concentrated, and purified by flash chromatography (hexane/ethyl acetate 90:10 as eluent) to give the corresponding alcohols.
With potassium phosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1,3-bis-(diphenylphosphino)propane; cesium fluoride at 50℃; for 5h; Inert atmosphere;
91%
With mesitylcopper(I); cesium fluoride; 1,4-di(diphenylphosphino)-butane; lithium tert-butoxide In diethyl ether at 20℃; for 18h; Inert atmosphere; Sealed tube;
With potassium phosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1,3-bis-(diphenylphosphino)propane; cesium fluoride at 50℃; for 5h; Inert atmosphere;
71%
With mesitylcopper(I); cesium fluoride; 1,4-di(diphenylphosphino)-butane; lithium tert-butoxide In diethyl ether at 20℃; for 18h; Inert atmosphere; Sealed tube;
57%
With potassium phosphate; Fe(1,2-bis(dimethylphosphino)ethane)2Cl2; cesium fluoride In tetrahydrofuran at 20℃; for 24h; Glovebox; Inert atmosphere;
Stage #1: benzylidene phenylamine With potassium phosphate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1,2-bis(dimethylphosphanyl)ethane; cesium fluoride In tetrahydrofuran for 0.166667h; Sealed tube;
Stage #2: benzaldehyde, hydrazone In tetrahydrofuran at 60℃; for 2h; Sealed tube;
71%
Stage #1: benzylidene phenylamine With potassium phosphate; [RhCl2(p-cymene)]2; tetrabutyl-ammonium chloride; triphenylphosphine In tetrahydrofuran at 20℃; for 0.166667h; Schlenk technique; Inert atmosphere; Green chemistry;
Stage #2: benzaldehyde, hydrazone In water at 70℃; for 1.5h; Schlenk technique; Inert atmosphere; Green chemistry;
General procedure for the synthesis of compounds 7
General procedure: A Schlenk tube (10 mL) equipped with a magnetic stir bar was charged with [Ru(p-cymene)Cl2]2 (1.8 mg, 0.003 mmol, 1.5 mol%), PPh3 (3.1 mg, 0.012 mmol, 6 mol%), K3PO4 (31.8 mg, 0.15 mmol, 0.75 equiv.), TBAC (11.1 mg, 0.04 mmol, 0.2 equiv.) and N-benzylideneaniline (0.2 mmol, 1.0 equiv.). The reaction system was then protected with an argon atmosphere. After that, THF (50 mL) was added and the reaction system was placed at room temperature. After stirring for 10 min, hydrazone (0.3 mmol, 1.5 equiv.) was added to the system. THF was removed in vacuo and argon was filled into the reaction system. Then, distilled water (0.2 mL) was added to the reaction system and heated to 70 °C. After stirring at 70 °C for 1.5 h, 3 mL water was added. After cooling to room temperature, 2 mL HCl solution (3 M) was added to the reaction system. The mixture was extracted with ethyl acetate (3x5 mL). The combined organic layers was washed with water (5 mL) and then dried over Na2SO4. The organic layers were concentrated and the resulting residue was purified by preparative TLC on silica gel to afford the product. 4.3.1. 1,2-diphenylethyl)benzenamine (7a) Colorless solid (38.7 mg, yield 71%); mp. 58-60 °C; Rf 0.54 (petroleum ether/dichloromethane 2/1); 1 H NMR (300 MHz, CDCl3) d 7.35-7.26 (m, 5H), 7.25-7.19 (m, 3H), 7.12 (d, J 6.4 Hz, 2H), 7.03 (d, J 8.4 Hz, 2H), 6.66-6.56 (m, 1H), 6.45 (d, J 7.7 Hz, 2H), 4.65-4.50 (m, 1H), 4.24-3.99 (m, 1H), 3.13 (dd, J 14.0, 5.7 Hz, 1H), 3.00 (dd, J 14.0, 8.2 Hz, 1H); 13C NMR (101 MHz, CDCl3) d 147.4, 143.6, 137.8, 129.4, 129.2, 128.71, 128.68, 127.2, 126.9, 126.6, 117.6, 113.8, 59.4, 45.3; HRMS (ESI, m/z), calcd for C20H20N [MH], 274.1590; found, 274.1587.
31%
With potassium phosphate; Fe(1,2-bis(dimethylphosphino)ethane)2Cl2; cesium fluoride In tetrahydrofuran at 20℃; for 24h; Glovebox; Inert atmosphere;
With bis(1,5-cyclooctadiene)nickel (0); 1,8-diazabicyclo[5.4.0]undec-7-ene; trimethylphosphane In tetrahydrofuran at 50℃; for 60h; Sealed tube; Inert atmosphere;
With bis(1,5-cyclooctadiene)nickel (0); 1,8-diazabicyclo[5.4.0]undec-7-ene; trimethylphosphane In tetrahydrofuran at 110℃; for 12h; Inert atmosphere; chemoselective reaction;
With bis(1,5-cyclooctadiene)nickel (0); 1,8-diazabicyclo[5.4.0]undec-7-ene; trimethylphosphane In tetrahydrofuran at 110℃; for 12h; Inert atmosphere; chemoselective reaction;
With bis(1,5-cyclooctadiene)nickel (0); 1,8-diazabicyclo[5.4.0]undec-7-ene; trimethylphosphane In tetrahydrofuran at 110℃; for 12h; Inert atmosphere; chemoselective reaction;
With hydrazine hydrate; In neat (no solvent); for 6h;Reflux;
General procedure: Amixture ofDHPMs a-h(0.01mol) and excess hydrazine hydrate (5 mL) was heatedunder reflux for 6 h. The reaction mixture was allowed tocool and poured on crushed ice.The obtained solid producta-d was filtered, crystallized from ethanol, and finallydried.The evaporation of the filtrate gave solid residue whichupon fractional crystallization from water gave the pyrazole and urea (a)/thiourea (b), respectively. 2.4.1. 3-Methyl-1H-pyrazol-5-ol (13). Yield: 42-55% (for a-h); m.p. 221-223 C (Lit. [49] m.p. 220-222 C); 1H-NMR(DMSO-6) delta (ppm): 2.47 (s, 3H, -CH3), 6.83 (s, 1H, Ar-H),10.07 (s, 1H, OH), 12.10 (s, 1H,NH).
With hydrazine hydrate; In neat (no solvent); for 6h;Reflux;
General procedure: Amixture ofDHPMs a-h(0.01mol) and excess hydrazine hydrate (5 mL) was heatedunder reflux for 6 h. The reaction mixture was allowed tocool and poured on crushed ice.The obtained solid producta-d was filtered, crystallized from ethanol, and finallydried.The evaporation of the filtrate gave solid residue whichupon fractional crystallization from water gave the pyrazole and urea (a)/thiourea (b), respectively. 2.4.1. 3-Methyl-1H-pyrazol-5-ol (13). Yield: 42-55% (for a-h); m.p. 221-223 C (Lit. [49] m.p. 220-222 C); 1H-NMR(DMSO-6) delta (ppm): 2.47 (s, 3H, -CH3), 6.83 (s, 1H, Ar-H),10.07 (s, 1H, OH), 12.10 (s, 1H,NH).
With tetrakis(pyridine)nickel dichloride; potassium <i>tert</i>-butylate; triphenylphosphine In 1,4-dioxane at 60℃; for 24h; Schlenk technique; Inert atmosphere;
51%
With nickel(II) bromide dimethoxyethane; lithium tert-butoxide; trimethylphosphane In 1,4-dioxane at 60℃; for 24h; Schlenk technique; Inert atmosphere;
With nickel(II) bromide dimethoxyethane; lithium tert-butoxide; trimethylphosphane In 2-methyltetrahydrofuran at 60℃; for 24h; Schlenk technique; Inert atmosphere;
52%
With nickel(II) bromide dimethoxyethane; lithium tert-butoxide; trimethylphosphane In 2-methyltetrahydrofuran at 60℃; for 24h; Schlenk technique; Inert atmosphere; Glovebox;
With nickel(II) bromide dimethoxyethane; lithium tert-butoxide; trimethylphosphane In 2-methyltetrahydrofuran at 60℃; for 24h; Schlenk technique; Inert atmosphere;
62%
With nickel(II) bromide dimethoxyethane; lithium tert-butoxide; trimethylphosphane In 1,4-dioxane at 60℃; for 24h; Schlenk technique; Inert atmosphere;
4-(4-bromophenyl)-3-phenyl-5-(trifluoromethyl)-4H-1,2,4-triazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
General procedure: Add sodium acetate, trifluoroethylimidyl chloride (II), hydrazone (III), and 1 mL of organic solvent to the 35 mL Schlenk tube according to the raw material ratio in Table 1.Mix and stir well. After the reaction is completed according to the reaction conditions in Table 2, 2-4 hours,Add elemental iodine, continue the reaction for 1-2 hours, filter, and stir the sample in silica gel.After purification by column chromatography, the corresponding 5-trifluoromethyl-substituted 1,2,4-triazole compound (I) is obtained. The reaction process is shown by the following formula:
3-phenyl-5-(trifluoromethyl)-4-(4-(trifluoromethyl)phenyl)-4H-1,2,4-triazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
General procedure: Add sodium acetate, trifluoroethylimidyl chloride (II), hydrazone (III), and 1 mL of organic solvent to the 35 mL Schlenk tube according to the raw material ratio in Table 1.Mix and stir well. After the reaction is completed according to the reaction conditions in Table 2, 2-4 hours,Add elemental iodine, continue the reaction for 1-2 hours, filter, and stir the sample in silica gel.After purification by column chromatography, the corresponding 5-trifluoromethyl-substituted 1,2,4-triazole compound (I) is obtained. The reaction process is shown by the following formula:
General procedure: Add sodium acetate, trifluoroethylimidyl chloride (II), hydrazone (III), and 1 mL of organic solvent to the 35 mL Schlenk tube according to the raw material ratio in Table 1.Mix and stir well. After the reaction is completed according to the reaction conditions in Table 2, 2-4 hours,Add elemental iodine, continue the reaction for 1-2 hours, filter, and stir the sample in silica gel.After purification by column chromatography, the corresponding 5-trifluoromethyl-substituted 1,2,4-triazole compound (I) is obtained. The reaction process is shown by the following formula:
N-(3-methylphenyl)-2,2,2-trifluoroacetimidoyl chloride[ No CAS ]
3-phenyl-4-(m-tolyl)-5-(trifluoromethyl)-4H-1,2,4-triazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
General procedure: Add sodium acetate, trifluoroethylimidyl chloride (II), hydrazone (III), and 1 mL of organic solvent to the 35 mL Schlenk tube according to the raw material ratio in Table 1.Mix and stir well. After the reaction is completed according to the reaction conditions in Table 2, 2-4 hours,Add elemental iodine, continue the reaction for 1-2 hours, filter, and stir the sample in silica gel.After purification by column chromatography, the corresponding 5-trifluoromethyl-substituted 1,2,4-triazole compound (I) is obtained. The reaction process is shown by the following formula:
4-(4-ethylphenyl)-3-phenyl-5-(trifluoromethyl)-4H-1,2,4-triazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
General procedure: Add sodium acetate, trifluoroethylimidyl chloride (II), hydrazone (III), and 1 mL of organic solvent to the 35 mL Schlenk tube according to the raw material ratio in Table 1.Mix and stir well. After the reaction is completed according to the reaction conditions in Table 2, 2-4 hours,Add elemental iodine, continue the reaction for 1-2 hours, filter, and stir the sample in silica gel.After purification by column chromatography, the corresponding 5-trifluoromethyl-substituted 1,2,4-triazole compound (I) is obtained. The reaction process is shown by the following formula:
4-(4-methoxyphenyl)-3-phenyl-5-(trifluoromethyl)-4H-1,2,4-triazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
General procedure: Add sodium acetate, trifluoroethylimidyl chloride (II), hydrazone (III), and 1 mL of organic solvent to the 35 mL Schlenk tube according to the raw material ratio in Table 1.Mix and stir well. After the reaction is completed according to the reaction conditions in Table 2, 2-4 hours,Add elemental iodine, continue the reaction for 1-2 hours, filter, and stir the sample in silica gel.After purification by column chromatography, the corresponding 5-trifluoromethyl-substituted 1,2,4-triazole compound (I) is obtained. The reaction process is shown by the following formula:
3-phenyl-4-(p-tolyl)-5-(trifluoromethyl)-4H-1,2,4-triazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
General procedure: Add sodium acetate, trifluoroethylimidyl chloride (II), hydrazone (III), and 1 mL of organic solvent to the 35 mL Schlenk tube according to the raw material ratio in Table 1.Mix and stir well. After the reaction is completed according to the reaction conditions in Table 2, 2-4 hours,Add elemental iodine, continue the reaction for 1-2 hours, filter, and stir the sample in silica gel.After purification by column chromatography, the corresponding 5-trifluoromethyl-substituted 1,2,4-triazole compound (I) is obtained. The reaction process is shown by the following formula:
With potassium phosphate; tris(triphenylphosphine)ruthenium(II) chloride; 1,1'-bis(dicyclohexylphosphinocyclopentadienyl)iron In 2-methyltetrahydrofuran at 40℃; for 24h; Sealed tube; Inert atmosphere;
With potassium phosphate; tris(triphenylphosphine)ruthenium(II) chloride; 1,1'-bis(dicyclohexylphosphinocyclopentadienyl)iron In 2-methyltetrahydrofuran at 40℃; for 24h; Sealed tube; Inert atmosphere;
1-(4-chlorophenyl)-3,4-diphenylbutan-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
46%
Stage #1: benzaldehyde, hydrazone With potassium phosphate; [RhCl2(p-cymene)]2; triphenylphosphine In tetrahydrofuran at 20℃; for 0.166667h; Schlenk technique; Inert atmosphere; Green chemistry;
Stage #2: 4'-chlorochalcone In water at 100℃; for 6h; Schlenk technique; Inert atmosphere; Green chemistry;
General procedure for the synthesis of compounds 3 and 4
General procedure: A Schlenk tube (10 mL) equipped with a magnetic stir bar was charged with [Ru(p-cymene)Cl2]2 (0.9 mg, 0.0015 mmol, 1.5 mol%), PPh3 (1.6 mg, 0.006 mmol, 6 mol%), K3PO4 (17 mg, 0.08 mmol, 0.8 equiv.), α,β-unsaturated ketone (0.1 mmol, 1.0 equiv.). The reaction system was then protected with an argon atmosphere. After that, THF (50 mL) was added to the reaction system. After stirring for 10 min at room temperature, hydrazone (0.25 mmol, 2.5 equiv.) was added to the system. THF was removed in vacuo and filled with argon. Then, distilled water (0.5 mL) was added to the reaction vessel and heated to 100 °C. The reaction system was stirred at 100 °C for 6 h and then diluted with 3 mL water. After cooling to room temperature, 2 mL HCl solution (3 M) was added to the reaction system, and the mixture was extracted with ethyl acetate (3x5 mL). The combined organic layers was washed with water (5 mL) and then dried over Na2SO4. The organic layers were concentrated and the resulting residue was purified by preparative TLC on silica gel to afford the product.
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1,2-bis(dimethylphosphanyl)ethane; lithium tert-butoxide In tetrahydrofuran at 80℃; for 12h; Inert atmosphere; regioselective reaction;
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; 1,2-bis(dimethylphosphanyl)ethane; lithium tert-butoxide In tetrahydrofuran at 80℃; for 12h; Inert atmosphere; regioselective reaction;
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