3-Fluoro-1,2-benzenediol

light beige to light brown-grey crystalline powder

3-fluorocatechol is a catechol bearing an additional fluoro substituent at position 3. It has a role as a bacterial xenobiotic metabolite and a fungal xenobiotic metabolite. It is a member of catechols, a member of monofluorobenzenes and a fluorophenol.

O-fluorophenol (20 g, 0.2 mol) was dissolved in acetonitrile (500 mL, dried over molecular sieves) and protected by argon. Anhydrous magnesium chloride (68 g, 0.72 mol) was added with stirring. Triethylamine (150 mL, 1.08 mol) was added and the mixture was exothermic. After stirring for 20 min, paraformaldehyde (42 g) was added and reacted at 50 ° C for 6 h. TLC showed that some of the starting material remained and the reaction time was not changed significantly. The temperature was lowered to room temperature, and a mixture of sodium hydroxide and water (22.8 g of sodium hydroxide dissolved in 80 mL of 7 jO) was added under ice-water bath. Hydrogen peroxide (30 wtpercent, 140 mL) was then slowly added dropwise with significant exotherm to keep the temperature below The reaction mixture was stirred at 30 ° C for 1.5 h, concentrated hydrochloric acid (12 mol / L) was added to adjust the pH value to 1, and the mixture was extracted with ethyl acetate (4 × 100 mL). The combined organic phases were added with saturated aqueous sodium thiosulfate (200 mL) The mixture was stirred for 1 h. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (1 × 100 mL). The combined organic phases were dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography (PE / EtOAc 15: 1 by volume as Eluent) to give 10.3 g of the pale yellow oily liquid (intermediate C-1a) in 45percent yield and recovery of o-fluorophenol 4.3goC-1a: 6H (300MHζ; CDC13) 6.63-6.45 (3H, m) (D, J = 15.5Ηζ), 120.3 (d, J = 15.5Ηζ) J = 8.9Hz), 111.6 (d, J = 2.6Hz), 108.1 (d, J = 18.4Hz)Under a nitrogen atmosphere, 600 mL of anhydrous tetrahydrofuran was added 16.2 mL of o-fluorophenol, 35 g of MgCl2, 50 mL of triethylamine and 16.2 g of paraformaldehyde were added and heated under reflux for 4 h.Cooled to room temperature, dropping 500mL0.05mol / L NaOH solution, all the components dissolved after the drop of 72mL 30percent hydrogen peroxide, the reaction 2h; then add 72mL 30percent H2O2, stirring reaction 6h.Then add 1.0mol / L hydrochloric acid, adjust the pH 4-5, extracted with methylene chloride, The extract was washed three times with 80percent aqueous Na2S2O3 and dried over anhydrous sodium sulfate overnight.The organic solvent was distilled off under reduced pressure, and the residue was separated by silica gel column chromatography, Eluting with methylene chloride and collecting the desired fractions and evaporated to dryness under reduced pressure to give 7.21 g of a crystalline solid as whiteUnder the protection of nitrogen, Add 16 mL of o-fluorophenol to 600 mL of anhydrous tetrahydrofuran.35g MgCl2, 50mL of triethylamine and 16g of paraformaldehyde, The reaction was heated to reflux for 4 h.Cool to room temperature, Add 500mL of 0.05mol/L NaOH solution dropwise.After all the components were dissolved, 72 mL of 30percent hydrogen peroxide was added dropwise.Reaction 2h;Add 70mL of 30percent H2O2, The reaction was stirred for 6 h.Then add 1.0 mol/L hydrochloric acid dropwise.Adjust the pH to 4-5, Extracted with dichloromethane, The extract was washed 3 times with an 80percent Na2S2O3 aqueous solution.It was dried over anhydrous sodium sulfate overnight.Evaporating the organic solvent under reduced pressure, The residue was separated by silica gel column chromatography.Elution with dichloromethane, Collect the required components, Evaporation to dryness under reduced pressure gave 7.5 g of white crystals.Intermediate 2.1) Synthesis of 3-fluorocatechol [H]: To a 500 ml flask were added 119 g (0.5 mol) of 2-fluoro-6-iodophenol and 200 ml of a 30percent aqueous potassium hydroxide solution and they were reacted under vigorous stirring under a reflux temperature for 8 hours. After the termination of the reaction, the mixture was cooled to ordinary temperature and neutralized with hydrochloric acid to adjust pH between 2 and 3. After filtration, the filtrate was washed with water to obtain 49.9 g of a product [H]. The process yield was 78percent.Synthesis of 1, 2-diethoxy-3-fluorobenzene [G1]; 2-Fluoro-6-iodophenol as a product of was hydrolyzed and then subjected to an etherification reaction to obtain 1, 2-diethoxy-3-fluorobenzene [G1].1) Synthesis of 3-fluorocatechol [H]:; To a 500 ml flask were added 119 g (0.5 mol) of 2-fluoro-6-iodophenol and 200 ml of a 30percent aqueous potassium hydroxide solution and they were reacted under vigorous stirring under a reflux temperature for 8 hours. After the termination of the reaction, the mixture was cooled to ordinary temperature and neutralized with hydrochloric acid to adjust pH between 2 and 3. After filtration, the filtrate was washed with water to obtain 49.9 g of a product [H]. The process yield was 78percent.To a 1 L dry reactor, a ligand compound a, a ligand compound b, a compound II, and a reaction solvent dimethyl sulfoxide were added under stirring.The molar ratio of the ligand compound a and the ligand compound b to the compound II is 1:1, the reaction temperature is 0 ° C, the reaction pressure is 0 MPa (gauge pressure), the reaction time is 18 hours, and the crude product is obtained after the reaction is completed. The crude product is further reacted with LiOH. After the completion of the reaction, the mixture is cooled to room temperature, and the insoluble material is filtered off. The filtrate is evaporated to dryness under reduced pressure, crystals are concentrated and dried to give a crude compound I.The crude product yield of compound I was 99.6percent and the crude product was 92percent pure.The recrystallization solvent was dimethyl sulfoxide, and the other reaction conditions were the same as in Example 1. The purity of the boutique is 99.90percent and the total yield is 99.0percent.The product has a chloride ion content <10ppm, a fluoride ion content <10ppm, a sulfate content <10ppm, a moisture content <10ppm, a metal content <10ppm, and other impurities <10ppm.

3-Fluorocatechol is a fluorinated catechol used in the preparation of synthetic humic acid as well as an intermediate in the preparation of 3-fluoroveratrole.

Molecular Weight:128.10
XLogP3:1.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Exact Mass:128.02735756
Monoisotopic Mass:128.02735756
Topological Polar Surface Area:40.5
Heavy Atom Count:9
Complexity:97.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes