3-tert-butyl-2-hydroxybenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 500 ml reactor thoroughly dried and purged with argon, 7.51 g (50 mmol) of 2-tert-butylphenol and 54 ml of THF were introduced. To the reactor, 18.53 ml of an ether solution containing 55.6 mmol of ethylmagnesium bromide was dropwise added at 0° C., then the temperature of the system was slowly raised to room temperature, and the reaction solution was stirred at room temperature for 1 hour. Then, 180 ml of toluene was added, and the system was heated to 100° C. to distill off about 40 ml of a mixed solution of ether and THF, whereby an opaque white slurry was obtained. After the slurry was cooled to room temperature, 3.75 g (125 mmol) of paraformaldehyde and 10.45 ml (75 mmol) of triethylamine were added, followed by stirring at 88° C. for 1 hour. The reaction solution was allowed to cool to room temperature and then quenched with 10% hydrochloric acid. The organic layer was concentrated and purified by a silica gel column to obtain 6.22 g (yield: 70%) of 3-t-butylsalicylaldehyde. Into a 500 ml reactor thoroughly dried were introduced was dropwise added at 0° C. the system was heated to 100° C. to distill off about 40 ml of a mixed solution of ether and THF, whereby an opaque white slurry was obtained After the slurry was cooled to room temperature by stirring at 88° C. for 1 hour to cool to room temperature quenched with 10% hydrochloric acid The organic layer was concentrated purified by a silica gel column

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-tert-butyl-2-hydroxybenzaldehyde (20 g, 74.53 mmol) in dichloromethane (400 mL) was treated with m-chloroperbenzoic acid (70%, 20 g) in 3 portions at room temperature. Stirring was continued overnight. The reaction mixture was diluted with dichloromethane (to 1 L) and washed with saturated sodium bicarbonate (2×400 mL) and water (500 mL). The organic layer was dried over sodium sulfate and filtered. The solvent was removed in a rotary evaporator. The residue was taken up in methanol (375 mL), potassium hydroxide (7.5 g) was added and this mixture was stirred at room temperature overnight. The solvent was removed in a rotary evaporator. The residue was taken up in water (250 mL) and made acidic with 6N hydrochloric acid. The aqueous phase was extracted with ethyl acetate (800 mL). The organic extract was washed with water (300 mL), dried over sodium sulfate and the solvent was removed in a rotary evaporator. The crude product was purified by chromatography on silica (350 g) with 5% ethyl acetate in heptane (4 L). Pure 9 (16 g, 83%) was isolated. washed with saturated sodium bicarbonate (2×400 mL) and water (500 mL) The organic layer was dried over sodium sulfate filtered The solvent was removed in a rotary evaporator potassium hydroxide (7.5 g) was added this mixture was stirred at room temperature overnight The solvent was removed in a rotary evaporator The aqueous phase was extracted with ethyl acetate (800 mL) The organic extract was washed with water (300 mL) dried over sodium sulfate the solvent was removed in a rotary evaporator The crude product was purified by chromatography on silica (350 g) with 5% ethyl acetate in heptane (4 L)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-tert-butylsalicylaldehyde (4)(3.56 g, 20 mmol) and paraformaldehyde (1.20 g, 40 mmol) was stirred with concentrated HCl (15 mL) for 14 days, although with the first drops of concentrated HCl, the emulsion became red. The mixture was then neutralized by treatment with a saturated solution of Na2CO3. The mixture was extracted with EtOAc (3×30 mL). Organic layers were dried over MgSO4 and the volatiles were evaporated under low pressure to give a beige solid which did not require further purification. Yield: 97%. Beige to red solid. 1H-NMR δH: 1.43 (9H, s, 3×CH3), 4.59 (2H, s, CH2), 7.43 (1H, d, J=2.1 Hz, HAr), 7.52 (1H, d, J=2.1 Hz, HAr), 9.87 (1H, s, CHO), 11.86 (1H, s, OH). The mixture was extracted with EtOAc (3×30 mL) Organic layers were dried over MgSO4 the volatiles were evaporated under low pressure to give a beige solid which purification