4-FLUORO-2-HYDROXYBENZALDEHYDE

Solid

To the mixture of 3-fluorophenol (10 mL, 102 mmole), anhydrous magnesium chloride (28.2 g, 744.6 mmole) in 500 mL of anhydrous acetonitrile was added anhydrous triethylamine (67 mL, 382. 5 mmole) and paraformaldehyde (22.3 g, 744.6 mmole). The mixture was then heated to reflux for five hours. After cooling to r. t, 500 mL of 5percent aqueous hydrochloric acid was added. The product was extracted with ethyl acetate. The combined organic extracts were washed with 5percent hydrochloric acid (x 3), brine, and dried over anhydrous magnesium sulfate. After removing the volatiles, the residue was a light pink solid. 11 g, yield 72percent. M. P: 67.5-69. 0°C. ESHRMS 777/Z 139.0211 (M-H, C7H4FO2 calc'd 139. 0201). 1H NMR (CDCl3/300MHz) 11.40 (s, 1H), 9.86 (s, 1H), 7.62-7. 57 (m, 1H), 6.79-6. 67 (m, 2H). 13C (CDC13/300MH) 195.4, 168.3 (d, J= 258 HZ), 164.4 (d, J=14. 9 Hz), 136.3 (d, J=12. 6 Hz), 118.2 (d, J= 2.0Hz), 108.5 (d, J= 23. 3 Hz), 104.9 (d, J=24. 4 HZ). L9F (CDCl3/400MHz) -97. 9 (m).To a mixture of 3-fluorophenol (415 mg, 3.70 mmol) and anhydrous MgCIExample 81 To a solution of 3-fluorophenol (2.0 mL, 22.3 mmol) and triethylamine (11.7 mmol) in anhydrous CH3CN (50 mL) was added p- formaldehyde (4.52 g, 151 mmol) and MgCl2 (3.19 g, 33.5 mmol) ML, 83.6 mmol). The reaction mixture was refluxed at 80 & lt; 0 & gt; C for 19 hours. After confirming the reaction with TLC, the reaction mixture was cooled to room temperature, and 3N HCl was added to the reaction mixture to adjust the pH to 2. The organic layer was extracted with ethyl acetate and distilled water and washed with brine. The separated organic layer was dried over anhydrous magnesium sulfate and then decompressed to remove the solvent. The reaction mixture was purified by flash column chromatography (CH2Cl2: Hex = 1: 1, Rf = 0.4) to obtain 4-fluoro-2-hydroxyaldehyde (1.97 g, 63percent, white solid).Preparation of intermediate (1) : 4-fluoro-2-hvdroxy-benzaldehyde: 4-Fluorophenol (5.0ml, 56.02mmol) and magnesium methoxide (44.5ml, 33.6mmol, 8percent wt in MeOH) were dissolved in methanol (30ml). Thereafter the reaction mixture was distilled until the methanol was left over about 15ml. thereto the reaction mixture was added toluene (42ml), and distilled when the reaction temperature was reached 95Step 1 4-Fluoro-2-hydroxy-benzaldehyde; To a solution of 3-fluorophenol (1 ml, 11 mmol) in THF(20 ml) in a three-neck flask was added ethylmagnesium bromide (5.5 ml, 5.5 mmol, IM in THF). After stirring at room temperature for 2 hours, benzene was added to the reaction mixture and THF was removed by distillation at 8OTo the mixture of 3-fluorophenol (5 mL, 51 mmol) , anhydrous magnesium chloride (14.1 g, 372 mmol) in 250 mL of acetonitrile was added triethylamine (34 mL, 190 mmol) and paraforaldehyde (11 g, 372 mmol) . The mixture was then heated to reflux for 5 hours. After cooling to room temperature, 250 mL of 5 HCl. aq was added, extracted with EA (100 mL×2) .

Molecular Weight:140.11
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:140.02735756
Monoisotopic Mass:140.02735756
Topological Polar Surface Area:37.3
Heavy Atom Count:10
Complexity:127
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes