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| | 4-FLUORO-2-METHOXYBENZALDEHYDE Basic information |
| | 4-FLUORO-2-METHOXYBENZALDEHYDE Chemical Properties |
| Melting point | 55 °C | | Boiling point | 224.6±20.0 °C(Predicted) | | density | 1.192±0.06 g/cm3(Predicted) | | storage temp. | under inert gas (nitrogen or Argon) at 2-8°C | | solubility | soluble in Methanol | | form | powder to lump | | color | White to Orange to Green | | Sensitive | Air Sensitive | | CAS DataBase Reference | 450-83-9(CAS DataBase Reference) |
| | 4-FLUORO-2-METHOXYBENZALDEHYDE Usage And Synthesis |
| Uses | 4-Fluoro-2-methoxy-benzaldehyde is used in the synthesis of imidazopyridazinones acting as novel PDE7 inhibitors for application towards Parkinson’s disease treatment. | | Synthesis | 3-Fluorophenol (20 g, 0.2 mol) was dissolved in molecular sieve-dried acetonitrile (500 mL), stirred under argon protection, and anhydrous magnesium chloride (102 g, 1.1 mol) was added. after 5 min, triethylamine (225 mL, 1.6 mol) was added, and an exothermic mixture was observed. After continued stirring for 30 min, paraformaldehyde (63 g) was added and the reaction was carried out for 3 h at 50 °C. Upon completion of the reaction, the pH was adjusted to 4 with 1N aqueous hydrochloric acid and the mixture was subsequently extracted with ethyl acetate (3 x 150 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 49.9 g of a dark red oily crude product (containing 4-fluoro-2-methoxybenzaldehyde and 2-fluoro-6-methoxybenzaldehyde), which was subsequently solidified. The crude product was dissolved in tetrahydrofuran (100 mL), potassium carbonate (81.2 g, 0.6 mol) and dimethyl sulfate (25.4 mL, 0.3 mol) were added, and the reaction was carried out at 40 °C overnight. Complete consumption of the raw materials was confirmed by TLC. Potassium carbonate was removed by filtration and the solid was washed with ethyl acetate (3 x 100 mL). The organic phases were combined, dried and concentrated with anhydrous magnesium sulfate. The residue was purified by column chromatography (eluent was petroleum ether/ethyl acetate, 15:1, v/v) to afford the intermediate 4-fluoro-2-methoxybenzaldehyde (15.8 g) and the by-product 2-fluoro-6-methoxybenzaldehyde (2.8 g), both as pale yellow solids, in an overall yield of 68%. 4-fluoro-2-methoxybenzaldehyde: melting point: °C; 1H NMR (300 MHz. CDCl3) δ 10.4 (1H, s), 7.85 (1H, dd, J = 8.4 Hz, 6.9 Hz), 6.75-6.67 (2H, m), 3.93 (3H, d, J =11.0 Hz), 13C NMR (75MHz, CDCl3) δ 130.9 (d, J =11.6 Hz), 121.6 (d, J = 2.7 Hz), 108.1 (d, J =22.1 Hz), 99.7 (d, J =25.7 Hz), 56.0. 2-Fluoro-6-methoxybenzaldehyde: melting point: 60-61 °C; 1H NMR (300 MHz, CDCl3) δ 10.3 (1H, s), 7.41 (1H, dd, J =15.0 Hz, 8.4 Hz), 6.71-6.61 (2.2). 6.71-6.61 (2H, m), 3.85 (3H, s), 13C NMR (75MHz, CDCl3) δ 187.4 (d, J = 3.4 Hz), 163.3 (d, J = 260.5 Hz), 162.2 (d, J = 5.4 Hz), 136.2 (d, J = 12.0 Hz), 114.0, 108.6 ( d, J = 21.3 Hz), 107.3 (d, J = 3.5 Hz), 56.3. | | References | [1] European Journal of Organic Chemistry, 2016, vol. 2016, # 7, p. 1429 - 1438
[2] Patent: CN104557654, 2017, B. Location in patent: Paragraph 0086-0088 |
| | 4-FLUORO-2-METHOXYBENZALDEHYDE Preparation Products And Raw materials |
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