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With sulfuric acid; nitric acid; at 27℃; for 6.0h;Cooling with ice;
To an ice-cold solution of 3-chloro-1-methyl-1H-pyrazole (42) (30 g, 0.26 mol) in concentrated sulfuric acid (50 mL) was slowly added fuming nitric acid (40 mL, 0.91 mol) drop wise. The resulting mixture was stirred at room temperature for 6 hours. After completion of reaction (TLC monitoring), the reaction mixture was poured into ice-cold water, the resulting solid was filtered and washed with pentane afforded the desired product (43) as yellow solid (30 g; Yield: 73%).1H-NMR (400 MHz, CDCl3): δ 8.16 (s, 1H), 3.94 (s, 3H).
With sulfuric acid; nitric acid; at 20℃; for 2.5h;Cooling with ice;
To a solution of 3-chloro-1-methylpyrazole (Maybridge, Basel, Switzerland, 953 mg, 8.18 mmol) in concentrated sulfuric acid (1.4 ml), cooled with an ice-bath, was added over 30 min fuming nitric acid (1 19 mL, 28.6 mmol). The reaction mixture was stirred at rt for 2 h before being poured on ice/water and extracted with EtOAc (2 x) The organic layers were washed with saturated aqueous NaHCO3 (2 x) and brine, dried over Na2SO4, filtered, evaporated and dried over vacuum to give the title compound as a white solid (HPLC tR 2 24 mm (Method A), M+H = 162 MS-ES)
3 g
With sulfuric acid; nitric acid; at 0 - 27℃; for 6.0h;
To a stirred solution of 3-chloro-1-methyl-1H-pyrazole 59 (4.0 g, 34 mmol) in Conc. H2S04 (4.0 mL) was added Fuming HNO3 (3.6 g, 120.0 mmol) dropwise at 0C and the mixture was stirred at RT for 6h. The mixture was then quenched slowly with ice, white solid precipitated out was filtered & dried over vacuum to obtain 3- chloro-1-methyl-4-nitro-1H-pyrazole (3.0 g, 54 % yield) as white solid. ‘HNMR (400 MHz, CDCl3): ö 8.16 (s, 1H), 3.94 (s, 3H).
With hydrogenchloride; sodium nitrite; In water; acetonitrile; at 0 - 25℃; for 16.0h;
Step 1: Into a 250 mL round bottom flask containing a solution of 1-methyl-4-nitro-1H-pyrazol-3-amine (4.0 g, 28 mmol) in acetonitrile (100 mL) was added concentrated hydrochloric acid (8mL) dropwise at 0 C. To this reaction mixture was added sodium nitrite (8.0 g, 116 mmol) inportions and the reaction mixture was gradually brought to room temperature and stirred for 16h. The reaction mixture was cooled to 0 C, treated with water (30 mL) and extracted with ethyl acetate (2x50 mL). The combined organics were washed with saturated sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with ethylacetate in petroleum ether (20-30%) to furnish 3-chloro-1-methyl-4-nitro-1H-pyrazole as a solid.‘H NMR (CDC13, 300 MHz): 5 8.25 (s, 1H), 3.98 (s, 3H).
With hydrogenchloride; sodium nitrite; In water; acetonitrile; at 0 - 25℃; for 16.0h;
Step 1: Into a 250 mL round bottom flask containing a solution of 1-methyl-4-nitro-1H-pyrazol- 3-amine (4.0 g, 28 mmol) in acetonitrile (100 mL) was added concentrated hydrochloric acid (8 mL) dropwise at 0 C. To this reaction mixture was added sodium nitrite (8.0 g, 116 mmol) in portions and the reaction mixture was gradually brought to room temperature and stirred for 16h. The reaction mixture was cooled to 0 C, treated with water (30 mL) and extracted with ethyl acetate (2x50 mL). The combined organics were washed with saturated sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with ethyl acetate in petroleum ether (20-30%) to furnish 3-chloro-1-methyl-4-nitro-1H-pyrazole as a solid.‘H NMR (CDC13, 300 MHz): 5 8.25 (s, 1H), 3.98 (s, 3H).
With hydrogenchloride; sodium nitrite; In water; acetonitrile; at 0 - 20℃; for 16.0h;
Step 1: Into a 250 mL round bottom flask containing a solution of l-methyl-4-nitro-lH-pyrazol- 3-amine (4.0 g, 28 mmol) in acetonitrile (100 mL) was added concentrated hydrochloric acid (8 mL) dropwise at 0 C. To this reaction mixture was added sodium nitrite (8.0 g, 116 mmol) in portions and the reaction mixture was gradually brought to room temperature and stirred for 16 h. The reaction mixture was cooled to 0 C, treated with water (30 mL) and extracted with ethyl acetate (2x50 mL). The combined organics were washed with saturated sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with ethyl acetate in petroleum ether (20-30%) to fumish 3-chloro-l-methyl-4-nitro-lH-pyrazole as a solid. 1H NMR (CDC13, 300 MHz): δ 8.25 (s, 1H), 3.98 (s, 3H).
With hydrogenchloride; sodium nitrite; In acetonitrile; at 0 - 20℃; for 16.0h;
Step 1: Into a 250 mL round bottom flask containing a solution of 1-methyl-4-nitro-1H-pyrazol- 3-amine (4.0 g, 28 mmol) in acetonitrile (100 mL) was added concentrated hydrochloric acid (8 mL) dropwise at 0 oC. To this reaction mixture was added sodium nitrite (8.0 g, 116 mmol) in portions and the reaction mixture was gradually brought to room temperature and stirred for 16 h. The reaction mixture was cooled to 0 oC, treated with water (30 mL) and extracted with ethyl acetate (2x50 mL). The combined organics were washed with saturated sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with ethyl acetate in petroleum ether (20-30%) to furnish 3-chloro-1-methyl-4-nitro-1H-pyrazole as a solid. 1H NMR (CDCl3, 300 MHz): δ 8.25 (s, 1H), 3.98 (s, 3H).
With N-chloro-succinimide; lithium hexamethyldisilazane; In tetrahydrofuran; at -78 - 20℃;Inert atmosphere;
The solution of compound 12 (11 g, 86.55mmol) and NCS(1.2 eq,13.87g, 103.85mmol) in dry THF (100 ml) was cooled to -78 C under N2. LiHMDS (1.5 eq, 26% in THF, 21.72g, 129.82mmol, 93.77mL) was added dropwise into the solution while the inner temperature was maintained at -78C. The reaction was stirred at same temperature for 2 h, and then warmed to room temperature and quenched with water (200 mL), extracted with EA, dried over anhydrous Na2SO4, filtered and evaporated. The residue was purified with column chromatography (PE:EA=20:1) to obtain the target compound 13 (7.0 g, 50 % yield).
3-(isopropylthio)-1-methyl-4-nitro-1H-pyrazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80.3%
With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 14.0h;Inert atmosphere;
The solution of compound 13 (7.0 g, 43.39mmol), propane-2-thiol (SM8, 3.97g, 52.07mmol) and K2CO3 (14.99g, 108.48mmol) in dry DMF (30mL) under N2 was stirred at 100C for 14 h. Then the solution was cooled to room temperature and quenched with water (100 mL), extracted with EA, dried over anhydrous Na2SO4, filtered and evaporated. The residue was purified with column chromatography (PE:EA=10:1) to obtain the target compound 14 (7.00 g, 80.3 % yield).
With hydrogenchloride; tetrakis(tetrabutylammonium)decatungstate(VI); In water; acetonitrile; at 20℃; for 24.0h;Glovebox; Sealed tube; Irradiation; Inert atmosphere;
General procedure: In a glovebox, the 1,3,5-trichloro-2-nitrobenzene(0.1 mmol, 1.0 equiv., 22.5 mg), TBADT (1 mol%, 3.3 mg), and cyclohexane (1 mmol, 5 equiv., 0.05 mL) were mixed in a sealed culture tube. Then degassed MeCN(1 mL) was added. HCl (0.3 mmol, 3.0 equiv., 0.03 mL) wasadded followed with a pipettor (avoid using metal material).The tube was set between two 50 W, 395 nm light-emitting diodes (LED, 3 cm away from the lamp) and stirred at roomtemperature (with a fan to cool down the reaction) for 24 h.After the reaction was completed, 5 mL of saturated aqueoussodium bicarbonate solution and 10 mL × 3 of ethyl acetatewere added and the combined organic layers were dried overNa2SO4. The solvent was removed under vacuum. The crudeproduct was purified by preparative thin layer chromatography(PTLC) to afford the corresponding product (hexane:ethyl acetate = 50:1).
With hydrogenchloride; tetrakis(tetrabutylammonium)decatungstate(VI); In water; acetonitrile; at 20℃; for 24.0h;Glovebox; Irradiation; Inert atmosphere;
General procedure: In a glovebox, the 1,3,5-trichloro-2-nitrobenzene(0.4 mmol, 1.0 equiv., 90 mg), TBADT (1 mol%,13.2 mg) were mixed in a Shrek tube. Then degassed MeCN(4 mL) was added. HCl (1.2 mmol, 3.0 equiv., 0.12 mL) wasadded with a pipettor (avoid using metal material). The reactiontube is placed and frozen with liquid nitrogen, andthen ventilated to make it full of propane gas (Figure S4, Supporting Information online). The tube was set betweentwo 50 W, 395 nm LED (3 cm away from the lamp) andstirred at room temperature (with a fan to cool down thereaction) for 24 h. After the reaction was completed (FigureS5), Zn (130 mg, 2 mmol, 20 equiv.) and 2N HCl (1 mL)were added to the reaction mixture. After stirring at 60 C foranother 1 h, the reaction mixture was cooled to room temperatureand filtered through Celite. After the filter cakewas washed with EtOAc, the filtrate was neutralized withsaturated NaHCO3 (aq.) and extracted with EtOAc threetimes. The combined organic layers were washed with brine,dried over Na2SO4, filtered, and concentrated under reducedpressure. The solvent was removed under vacuum. The crudeproduct was purified by PTLC to afford the correspondingproduct (hexane:ethyl acetate = 50:1).
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