4-Fluoro-2-methoxybenzaldehyde

The m-fluorophenol (20g, 0.2πο1) was dissolved in acetonitrile (500mL, dried over molecular sieves), protected by argon and anhydrous magnesium chloride (102g, l.lmol) was added with stirring. 5min. Triethylamine (225 mL, 1.6 mol) was added and the mixture was exothermic. After stirring for 30 min, paraformaldehyde (63 g, purchased from aldrich company, the same below) was added and reacted at 50 ° C. for 3 h. Finished reaction. 1N aqueous hydrochloric acid was added to adjust the pH to 4, and the mixture was extracted with ethyl acetate (3 × 150 mL). The combined organic phases were dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure (water chestnut) to give the crude product as a dark red oil B-la and aldehyde by-product) 49.9g, set curing. The crude product was dissolved in tetrahydrofuran (100 mL) and potassium carbonate (81.2 g, 0.6 mol) and dimethyl sulfate (25.4 mL, 0.3 mol) were added and reacted at 40 ° C overnight ), TLC showed the raw material has disappeared. The potassium carbonate was filtered off and the solid was washed with ethyl acetate (3 × 100 mL). The organic phases were combined, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography (using a 15: 1 volume ratio of ro / Et0Ac as eluant) Intermediate B-2a (15.8 g) and by-product 2-fluoro-6-methoxybenzaldehyde (2.8 g) all in the form of a light yellow solid with a total yield of 68percent 0B-2a: Mp: ° C; 6h (300ΜΗζ; CDC13) 10.4 (1Η, s), 7.85 (1Η, dd, J = 8.4Hz, 6.9Ηζ), 6.75-6.67 (2H, m), 3.93 (d, J = 11.0Ηζ), 130.9 (d, J = 11.6Ηζ), 121.6 (d, J = , J = 2.7Hz), 108.1 (d, J = 22.1Ηζ), 99.7 (d, J = 25.7Ηζ), 56.0.2-Fluoro-6-methoxy- benzaldehyde: Μρ: 60-61 ° C ; 6H (300 MΗζ; CDC13) 10.3 (1H, s), 7.41 (1H, dd, J = 15.0Ηζ, 8.4Ηζ), 6.71-6.61 (2H, m), 3.85 (3H, s) CDC13) 187.4 (d, J = 3.4 Hz), 163.3 (dJc, F = 260.5 Hz), 162.2 (d, J = 5.4Ηζ), 136.2 (d, J = 12.0Ηζ), 114.0 ), 108.6 (d, J = 21.3 Hz), 107.3 (d, J = 3.5Ηζ), 56.3.A DMF (2 mL) solution of General procedure: To a suspension of hydrazide 4 (0.25 g, 1 mmol) in absolute ethanol (3 ml), aromatic aldehyde (2 mmol) was added. The reaction mixture was heated under reflux for 15 h. When the reaction was completed as shown by TLC, the reaction mixture was cooled to room temperature, the precipitated solid was collected by filtration, washed twice with ethyl acetate, carefully dried and recrystallized from acetonitrile. 1H NMR spectra of all separated schiff bases showed two conformers in different ratios ranging from 1:1 to 1.8:1.

Molecular Weight:154.14
XLogP3:1.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:154.04300762
Monoisotopic Mass:154.04300762
Topological Polar Surface Area:26.3
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes