1,3-Dichloro-2-fluoro-4-nitrobenzene

2, 6-dichlorofluorobenzene was dissolved in 20percent methylene chloride, Flat streamerUsed to enter the nitric acid, Set the flow rate to11.9ml/min corresponding to nitric acid 0.27ml , Flat streamer 13 used to enter the sulfuric acid, Set the flow rate of 25.2ml, equivalent to sulfuric acid 0.46mol / min, Sulfuric acid and nitric acid in a microchannel reactor1 to complete the mix, Flat streamerC used to enter2, 6-dichlorofluorobenzene in methylene chloride at a flow rate of 38.5 ml / min, Equivalent to 2, 6-dichlorofluorobenzene 0.27 mol / min, 2, 6-dichlorofluorobenzene and mixed acid in the microchannel reactor 2 to start the mixing reaction, At this time, the molar ratio of 2, 6 - dichlorofluorobenzene to nitric acid was 1: 1, the reaction temperature was 40 ° C, The reaction residence time in each microchannel reactor was 33 s and the system pressure was 0.7 MPa.After the product was withdrawn from the outlet, the conversion of 2, 6-dichlorofluorobenzene was 100percent after extraction, washing and washing, and the selectivity of 2, 4-dichloro-3-fluoronitrobenzene was 94percent.Step 2, with a thermometer, Blender, Adding solvent to the three-necked flask of the reflux condenserNitrification, PTC and dried KF, Stir under heating, react for 7 h, cool and filter, DMF is recovered at atmospheric pressure, followed by steam distillation. The distillate was extracted with ethyl acetate and dried over anhydrous Na2SO4.After recovering ethyl acetate under normal pressure, The distillation was carried out under reduced pressure to collect 92-93 C fractions.That is, the reaction temperature is 160 to 165 C.The yield is about 85%.Intermediate 43 4- chloro-3-fluorobenzene-l, 2-diamine A microwave tube was charged with l , 3-dichloro-2-fluoro-4-nitrobenzene (2.00 g, 9.52 mmol), phenylmethanamine (4.17 mL, 38.1 mmol) and THF (20 mL). The reaction mixture was heated in the microwave at 80C for 3 h before being concentrated. The residue was dissolved in EtOAc (40 mL) and washed with 0.5M HCl(aq) (20 mL) and then brine (20 mL). The organic phase was dried (Na2S04), filtered and concentrated. The residue was dissolved in MeOH (15 mL) and the flask was evacuated and flushed with nitrogen (x 3). 10% Pd/C (60 mg, 0.06 mmol) was added to the stirred solution. The flask was evacuated and flushed with nitrogen (x 3) and then evacuated and flushed with hydrogen (x 3). After stirring for 18 h the reaction was filtered through celite, rinsed with EtOH and concentrated to give the crude product as a brown solid. The crude product was purified by silica chromatography, using 20-60% EtOAc in heptane as eluent, to give the title compound as a reddish-brown solid (655 mg, 72%); m/z = 160.9, 162.9 (MH)+.General procedure: 2-Chloro-3-fluoro-6-nitrobenzene-1-thiol Sodium sulfide (7.26 g, 93.0 mmol) was added to a stirred solution of 2-chloro-l, 3- difluoro-4-nitrobenzene (5.00 g, 25.8 mmol) in DMSO (100 mL). The reaction was allowed to stir at room temperature for 18 h then the reaction mixture was diluted with water (500 mL), and acidified to pH 1 -2 by the addition of 50% aqueous HC1. The mixture was then extracted with EtOAc (3 x 120 mL). The combined organic extracts were washed with brine (50 mL), dried over sodium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was purified by FCC over silica (eluent: heptane:EtOAc 1 :0 to 85:15) affording the title compound as fine yellow needles (1.98 g, 35% yield); 1H NMR (500 MHz, Chlorofom-d) delta 7.10 (dd, 1H), 8.26 (dd, 1H).2, 6-dichlorofluorobenzene was dissolved in 20% methylene chloride, Flat streamerUsed to enter the nitric acid, Set the flow rate to11.9ml/min corresponding to nitric acid 0.27ml , Flat streamer 13 used to enter the sulfuric acid, Set the flow rate of 25.2ml, equivalent to sulfuric acid 0.46mol / min, Sulfuric acid and nitric acid in a microchannel reactor1 to complete the mix, Flat streamerC used to enter2, 6-dichlorofluorobenzene in methylene chloride at a flow rate of 38.5 ml / min, Equivalent to 2, 6-dichlorofluorobenzene 0.27 mol / min, 2, 6-dichlorofluorobenzene and mixed acid in the microchannel reactor 2 to start the mixing reaction, At this time, the molar ratio of 2, 6 - dichlorofluorobenzene to nitric acid was 1: 1, the reaction temperature was 40 C, The reaction residence time in each microchannel reactor was 33 s and the system pressure was 0.7 MPa.After the product was withdrawn from the outlet, the conversion of 2, 6-dichlorofluorobenzene was 100% after extraction, washing and washing, and the selectivity of Weigh a certain amount of 2, 6-dichlorofluorobenzene in the flask, Add some concentrated sulfuric acid and a small amount of anhydrous Na2SO4 under heating and stirring, and stir to 60-70 C to dissolve completely.Then cool to 50 ~ 55 C, start slowly adding mixed acid, Reaction 2 h, After the reaction is completed, let stand for another 3 to 4 hours.The product was rinsed with 10% NaOH and cold water.The aqueous layer was extracted with anhydrous ethyl ether and dried over anhydrous sodium sulfate.The desiccant is filtered off, and the ether is recovered by atmospheric distillation.Distilling under reduced pressure to take the middle fraction, Distillation temperature 117 ~ 119 C, Obtained a pale yellow oil which is EXAMPLE 7 2, 3, 4-Trifluoronitrobenzene In a 2.5 liter flange flask fitted with a distillation bridge and anchor stirrer, 488 g (8.4 mol) of potassium fluoride, 40.0 g (0.06 mol) of trimethyl(ethoxypolyoxypropyl methyl ether)ammonium chloride, 20.0 g (0.04 mol) of polyethylene glycol dimethyl ether 500 and 20.4 g (0.06 mol) of tetrabutylphosphonium bromide were introduced at 110 C. into the melt of 840 g (4 mol) of

Molecular Weight:209.99
XLogP3:3.1
Hydrogen Bond Acceptor Count:3
Exact Mass:208.9446619
Monoisotopic Mass:208.9446619
Topological Polar Surface Area:45.8
Heavy Atom Count:12
Complexity:187
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes