1) Metal-free DBU promoted cycloaddition of styrene to hydroxylimine

SyntheticPage 773
Published Jan 06, 2015

Procedure

Preparation of 4-hydroxy phenylaldoxime: To the solution of hydroxylamine hydrochloride (1 g, 14.5 mmol) in water (10 ml) was added sodium hydroxide (307 mg, 7.6 mmol) and 4-hydroxy benzaldehyde (1.77 g, 14.5 mmol) and reaction mixture was stirred for 2 hrs at room temperature. After completion of the reaction (monitoring by TLC), if compound precipitated out, was filtered on Buckner funnel or extracted with EtOAc (3 ´ 15 ml). The obtained product was taken for next step without further purification (> 90% yield).

Procedure for synthesis of 3-(4-hydroxy phenyl) 5-phenyl-isoxazole: To the stirred solution of 4-hydroxy phenyl aldoxime (100 mg, 0.729 mmol) in DMF (3 ml) was added N-chlorosuccinimide (161 mg, 0.875 mmol) at room temperature and reaction was stirred for 0.5 h. Then, DBU (111 mg, 0.729 mmol) and styrene (91 mg, 0.875 mmol) were added and reaction was further stirred for 1 h. After completion of the reaction (confirmed by TLC), chilled water (20 ml) was added and product was extracted with EtOAc (3 ´ 10 ml). The organic layer was collected, dried on anhydrous sodium sulphate and solvent was evaporated on rotary evaporator to get the crude product. The crude product was purified by silica gel (#100-200) column chromatography using 20% EtOAc: hexane to get title compound as a white solid (138 mg; 80% yield).

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2) Etherification of 4-Hydroxybenzaldehyde with a benzyl bromide

SyntheticPage 836
Published Jun 09, 2018

Procedure

A solution of 4-hydroxybenzaldhyde (2.0 g, 16.4 mmol), 4-nitrobenzyl bromide (3.54 g, 16.4 mmol), potassium carbonate (3.40 g, 24.6 mmol) in dry DMF (20 mL) was heated at 100℃ for 3 h with constant stirring. The reaction mixture was allowed to cool, added to ice water and the resulting precipitate was isolated at the pump to give a yellow solid. The solid was washed three times with water (10 mL each time) to yield 4-(4-nitrobenzyloxy)benzaldehyde (3.11 g, 74%) as a light yellow solid. [How was it dried?]

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3) Etherification of 4-hydroxybenzaldhyde with propargyl bromide

SyntheticPage 838
Published Jun 17, 2018

Procedure

A solution of 4-hydroxybenzaldhyde (3.03 g, 25 mmol), propargyl bromide (11.61g, 98 mmol), and potassium carbonate (13.55 g, 98 mmol) in acetone (250 mL) was heated at reflux for 4 h with constant stirring. Upon cooling, the reaction mixture was transferred to a separating funnel along with distilled water (50 mL) and DCM (30 mL). The product was extracted into the organic layer, isolated and dried over sodium sulphate. The solvent was removed under reduced pressure to yield 4-(prop-2-yn-1-yloxy)benzaldehyde (3.26 g, 82 %) as a pale orange solid.

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