1,2-DIMETHOXY-4-FLUOROBENZENE

white to light yellow crystal

General procedure: 14 Typical continuous diazotization procedure: Material A (50 mL of aqueous solution containing amine (100 mmol), fluoroboric acid (120 mmol), hydrochloric acid (180 mmol)), and material B (50 mL of aqueous solution containing sodium nitrite (105 mmol)) were pumped into the T-joint at 4 mL/min, respectively, after a residence time of about 15 s at 25 °C in a reacting tube, the mixture flowed through the outlet and accumulated in the cooling vessel. Vigorous stirring was maintained. The solid was filtered with suction after the slurry was cooled to −5 °C. The solid was washed with methanol and then dried in vacuo to yield the corresponding diazonium tetrafluoroborate. 15 Typical continuous fluorodediazoniation procedure: Slurry of the diazonium tetrafluoroborate prepared as above in 300 mL of cosolvent was introduced into a reacting tube continuously at a flow rate of 4 mL/min. The mixture was maintained for 1 min at setting temperature and then cooled in the tandem tube. The collected liquid was washed with aqueous NaOH and water, nearly colorless liquid was obtained.A reaction vessel equipped with a stirrer, a thermometer and a dropping funnel was charged with 70 mL of a 50percent ethyl difluoroiodoacetate solution, Ketone 50mL, 3, 4-dimethoxyaniline slowly added 0.07mol, dissolved, reduce the solution temperature to 6 , control the stirring speed at 200rpm, Adding 60 mL of isobutyl sulfite 20 mL, stirring continued for 50 min, adding ethyl acetate 300 mL, reducing the solution temperature to5 ° C, precipitated solid after filtration, washed with 1, 2-dichloroethane, vacuum drying, in fluoride acid diazonium salt;(Ii) adding 0.13 mol of the diazonium salt of fluoroiodo acid obtained in step (i) to a reaction vessel, and installing a distillation apparatus to receive the bottle temperature at 9 ° C, The reaction solution was heated and the temperature was controlled at 90 ° C to decompose the reactants. A brown oily liquid was collected, dissolved in benzene, washed with sodium carbonateLiquid washing, sodium bromide solution washing, water layer with ethyl eye solution extraction, combined with benzene dissolved layer, anhydrous sodium sulfate dehydration, steaming solvent, 1.7kPaVacuum distillation, collection 85-90 ° C distillate, 3, 4-dimethoxyfluorobenzene 5.02g, yield 46percentGeneral procedure: A 0.10 M THF solution of 2-(trimethylsilyl) phenylnonaflate 3 (1.0 equiv) and a 0.22 M THF solution of Bu4NF(t-BuOH)4 (2.2 equiv) were m ixed a nd reacted at room temperaturein a continuous flow reactor consisting of a dual syringepump set to 5.0 mL/min, a Comet X-01 mixing element, and an outlet tube (inner diameter 0.96 mm, outer diameter1.56 mm, length 224 cm, and residence volume 1.62 mL). Theeffective residence time was 9.7 s. The crude reaction mixturewas collected into a test tube containing ca. 1 mL of a saturatedNH4Cl solution for 24 s [total volume 4.0 mL, 0.20 mmol of3, 0.44 mmol of Bu4NF(t-BuOH)4] from at least 10 s after thecommencement of solution flow. The mixture was extractedwith hexane and washed with water. The aqueous phase wasextracted twice with hexane. The combined organic phasewas washed with a saturated NaCl solution and dried overanhydrous Na2SO4. The mixture was filtered and the solventwas removed under reduced pressure. The crude product waspurified by silica-gel flash column chromatography (eluent:hexane, a mixture of hexane and EtOAc, or CH2Cl2) to affordthe fluorinated product 1....presented by the following formula (4) which can respectively correspond to the formula (1) can be obtained. (D) Fluorine substituted aromatic compound represented by the formula (4) corresponding to the hydroxy compound wherein X1 is a substituent of the group (a) in the formula(1): ... 2-methoxyfluorobenzene, 3-methoxyfluorobenzene, 4-methoxyfluorobenzene, 2-ethoxyfluorobenzene, 3-ethoxyfluorobenzene, 4-ethoxyfluorobenzene, 2, 3-dimethoxyfluorobenzene, 2, 6-dimethoxyfluorobenzene, General procedure: To a 4 ml borosilicate vial, equipped with a stir bar, was added Ir[dF(CF3)ppy]2(dtbpy)PF6 (2.4 mg, 2.1 mumol, 1.0 mol%) (dF(CF3)ppy, 2-(2, 4-difluorophenyl)-5-(trifluoromethyl)pyridine; dtbpy, 4, 4'-di-tert-butyl-2, 2'-bipyridine)) and an aryl (tetrafluoro)thianthrenium salt (0.200 mmol, 1.00 equiv.). Under N2 atmosphere, Cu(MeCN)4BF4 (94.4 mg, 0.300 mmol, 1.50 equiv.), anhydrous CsF (36.4 mg, 0.240 mmol, 1.20 equiv.) and anhydrous acetone (2.0 ml, 0.10 M) were added into the reaction vial. Subsequently, the vial was capped and placed 5 cm away from two 34 W blue light-emitting diode (LEDs). The temperature was kept at approximately 30 C through cooling with a fan. After being stirred for 20 h, the reaction mixture was diluted with CH2Cl2 (2 ml) and the resulting mixture was filtered through a short pad of Celite using CH2Cl2 (5 ml) as eluent. The filtrate was collected and concentrated by rotary evaporation. The residue was purified by chromatography on silica gel to afford the fluorinated product. Note that for the optimal results, the use of anhydrous CsF is important for the reaction. When CsF was weighed under ambient atmosphere, the yield of the fluorinated product was lower and the yield of the hydrodefunctionalized product was higher. Schlenk techniques can be used to avoid moisture. For convenience, we stored and weighed the CsF in a N2-filled glove box; the reactions can be performed outside a glove box.

Molecular Weight:156.15
XLogP3:2.2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:156.05865769
Monoisotopic Mass:156.05865769
Topological Polar Surface Area:18.5
Heavy Atom Count:11
Complexity:119
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes