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CAS No. : | 103877-80-1 | MDL No. : | MFCD08063230 |
Formula : | C8H6F2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PWWMQUUDAAWEBK-UHFFFAOYSA-N |
M.W : | 172.13 | Pubchem ID : | 13657451 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; | Preparation of 2,5-difluoro-4-methyl-benzoyl chloride 250 ml of thionyl chloride are taken and 120 g of <strong>[103877-80-1]2,5-difluoro-4-methyl-benzoic acid</strong> are introduced in portions at room temperature, with brisk evolution of gas. When the evolution of gas has subsided, the mixture is heated slowly to the reflux temperature and stirred until the evolution of gas has ended. The excess thionyl chloride is distilled off, the reaction product is coarsely distilled over and the distillate is fractionated on a small column. Yield: 97 g (72.9% of theory) of 2,5-difluoro-4-methylbenzoyl chloride of boiling point b.p.: 103/20 mbar, nD20: 1.5232. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 18h;Inert atmosphere; Reflux; | Preparation 32,5-Difluoro-4-methyl-N-(methylsulfonyl)benzamideA mixture of <strong>[103877-80-1]2-5-difluoro-4-methylbenzoic acid</strong> (6.0 g, 34.9 mmol), diisopropylethylamine (13.5 g, 105.0 mmol), propanephosphonic acid cyclic anhydride (50 mL, 50% w/w solution in ethyl acetate, 84.0 mmol) and methyl sulphonamide (6.6 g, 69.7 mmol) in tetrahydrofuran (200 mL) was heated under reflux with stirring under N2 for 18 hours. After cooling, the solution was evaporated in vacuo and the residue suspended in water. The mixture was extracted with ethyl acetate (300 mL) and the organic extract then washed with brine (2 x 80 mL). The organic solution was then dried over sodium sulphate and evaporated in vacuo to give a solid. Trituration with hexane gave the title compound (7.6 g, 87%) as an off white solid after drying.1H NMR (400 MHz, d6-DMSO): delta 2.26 (s, 3H), 3.34 (s, 3H), 7.33 (m, 1 H), 7.44 (m, 1 H). LCMS Rt = 1 .24 minutes MS m/z 248 [M-H]- |
87% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; ethyl acetate; for 18h;Reflux; Inert atmosphere; | Preparation 92,5-Difluoro- -methyl-N-(methylsulfonyl)benzamideA mixture of <strong>[103877-80-1]2-5-difluoro-4-methylbenzoic acid</strong> (6.0 g, 34.9 mmol), diisopropylethylamine (1 3.5 g, 1 05.0 mmol), propanephosphonic acid cyclic anhydride (50 mL, 50% w/w solution in ethyl acetate, 84.0 mmol) and methyl sulphonamide (6.6 g, 69.7 mmol) in THF (200 ml_) was heated under reflux with stirring under N2 for 18 hours. After cooling, the solution was evaporated in vacuo and the residue suspended in water. The mixture was extracted with ethyl acetate (300 ml_) and the organic extract then washed with brine (2 x 80 ml_). The organic solution was then dried over sodium sulphate and evaporated in vacuo to give a solid. Trituration with hexane gave the title compound (7.6 g, 87%) as an off white solid after drying.1H NMR (400 MHz, DMSO-d6): delta 2.26 (s, 3H), 3.34 (s, 3H), 7.33 (m, 1 H), 7.44 (m, 1 H). LCMS Rt = 1 .24 minutes. MS m/z 248 [M-H]- |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sulfuric acid; for 18h;Reflux; | Preparation 18Ethyl 2 ,5-difl uoro-4-meth yl benzoateTo a solution of <strong>[103877-80-1]2,5-difluoro-4-methylbenzoic acid</strong> (5 g, 2.904 mmol) in ethanol (100 ml_) was added concentrated sulfuric acid (1 ml_). The reaction mixture was stirred at reflux for 18 hours. LCMS showed complete consumption of starting material, so the solvents were removed in vacuo and the resulting residue redissolved in EtOAc (50 ml_), and washed with saturated aqueous sodium bicarbonate. The organic layer was separated, and the aqueous layer extracted with EtOAc (2 x 50 ml_). The combined organics were dried over sodium sulfate and evaporated to yield the title compound as a pale yellow oil (5.502 g, 95%).1H NMR (CDCIs, 400 MHz): delta 1 .38 (t, 3H), 2.30 (d, 3H), 4.37 (q, 2H), 6.95 (dd, 1 H), 7.55 (dd, 1 H).LCMS Rt = 3.06 minutes. MS m/z molecular ion not observed. |
With thionyl chloride; at 70℃; for 18h; | To a solution of <strong>[103877-80-1]2,5-difluoro-4-methylbenzoic acid</strong> (595 mg, 3.89 mmol) in ethanol (30 ml_) was added a catalytic amount of thionyl chloride (2 drops). The reaction was stirred for 18 hours at 70 C, and cooled to room temperature. The solvent was removed in vacuo to afford the title compound as a clear oil (500 mg, 86%). No further purification undertaken. 1H NMR (400 MHz, CDCI3): delta 1 .30 (t, 3H), 2.30 (s, 3H), 4.40 (q, 2H), 6.90 (m, 1 H), 7.60 (m, 1 H). LCMS Rt = 3.53 minutes MS no mass ion observed. |
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