6-Chloro-2,3-dihydro-4H-1-benzopyran-4-one

White solid

A mixture of 11 (2 g, 10 mmol) and concentrated sulfuric acid (20 mL) was stirred at room temperature for 1 h, poured onto ice and extracted with ethyl acetate. The organic layer was washed twice with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered, and evaporated under vacuum. The title product was recrystallized in ethyl acetate/hexane (1:5). The resulting precipitate was collected by filtration, washed with hexane, and dried (1 g, 55percent): mp 98-101 °C (lit. [31]: mp 100-101 °C); In a dry three-necked flask into DMF (0.35 mol), ice bath cooling to 0-5 C, POCl3 (0.30 mol) was slowly added dropwise with stirring, during the dropwise addition, the reaction temperature is not more than 5 C, after the addition was complete, stirring was continued for 0-5 C maintained for 1 hour; then, at 10 C, a solution of General procedure: In a 50 mL flask, phenol (30 mmol) and acrylonitrile (33 mmol) were added to the flask, and then 1 mL triethylamine was added to the flask and stirred for 24 h under reflux. The reaction system was added with ethyl ether, then washed with NaOH aq. (20% wt.) and 2N HCl aq. and then dried with anhydrous sodium sulfate. Then the organic phase was concentrated under reduced pressure, and the resulting residue was added with about 40 mL conc. HCl and refluxed with several hours. The reaction system was extracted with ethyl acetate three times and then dried with anhydrous sodium sulfate. Then the organic phase was concentrated under reduced pressure without further purification. To the solution of carboxylic acid (10 mmol) in dry CH2Cl2 (50 mL) was added 0.2 mL of DMF at 0 C. Oxalyl chloride (15 mmol) was then added dropwise under nitrogen atmosphere at 0 C. The reacion was stirred at 0 C for 16 h and the mixture was concentrated at high vacuum to give the desired acid chloride, which was directly use without further purification. To the acid chloride in dry CH2Cl2 (50 mL) was added AlCl3 (15 mmol) slowly under a positive atmosphere of nitrogen 0 C. The mixture was stirred at 0 C overnight. The mixtures were quenched with water followed by extraction with CH2Cl2 . The combined organic layer was dried over anhydrous Na2SO4 , filtered and concentrated. The residue was purified by column chromatography to give corresponding ketone. A 50 mL oven-dried schlenk flask containing a magnetic stir bar was charged with sodium hydride (dry, 60%, 0.48 g, 2.0 equiv) and capped with a septum. The reaction flask was evacuated and backfilled with argon (this process was repeated a total of three times), and the flask was equipped with a balloon filled with argon. THF (10 mL) was added to the flask, and the mixture was cooled down to 0 C in an ice bath. Triethylphosphonoacetate (2.8 g, 2.5 mL, 2.0 equiv) was then added dropwise via syringe to the suspension of sodium hydride over 15 minutes, and the mixture was stirred for 30 min. The solution of corresponding ketone (6 mmol, 1.0 equiv) in THF (10 mL) was then added to the reaction flask via syringe at 0 C. The reaction mixture was allowed to warm to 60 C (detected by TLC analysis). The septum and the balloon were removed, and the reaction was carefully quenched by the slow addition of aqueous sat. NH4Cl solution. The mixture was then extracted with ethyl acetate (3×), washed with brine, dried with Na2SO4 , filtered, concentrated in vacuo and purified by silica gel chromatography to afford the corresponding alpha, beta-unsaturated ester.General procedure: In a 50 mL flask, phenol (30 mmol) and acrylonitrile (33 mmol) were added to the flask, and then 1 mL triethylamine was added to the flask and stirred for 24 h under reflux. The reaction system was added with ethyl ether, then washed with NaOH aq. (20% wt.) and 2N HCl aq. and then dried with anhydrous sodium sulfate. Then the organic phase was concentrated under reduced pressure, and the resulting residue was added with about 40 mL conc. HCl and refluxed with several hours. The reaction system was extracted with ethyl acetate three times and then dried with anhydrous sodium sulfate. Then the organic phase was concentrated under reduced pressure without further purification. To the solution of carboxylic acid (10 mmol) in dry CH2Cl2 (50 mL) was added 0.2 mL of DMF at 0 C. Oxalyl chloride (15 mmol) was then added dropwise under nitrogen atmosphere at 0 C. The reacion was stirred at 0 C for 16 h and the mixture was concentrated at high vacuum to give the desired acid chloride, which was directly use without further purification. To the acid chloride in dry CH2Cl2 (50 mL) was added AlCl3 (15 mmol) slowly under a positive atmosphere of nitrogen 0 C. The mixture was stirred at 0 C overnight. The mixtures were quenched with water followed by extraction with CH2Cl2 . The combined organic layer was dried over anhydrous Na2SO4 , filtered and concentrated. The residue was purified by column chromatography to give corresponding ketone. A 50 mL oven-dried schlenk flask containing a magnetic stir bar was charged with sodium hydride (dry, 60%, 0.48 g, 2.0 equiv) and capped with a septum. The reaction flask was evacuated and backfilled with argon (this process was repeated a total of three times), and the flask was equipped with a balloon filled with argon. THF (10 mL) was added to the flask, and the mixture was cooled down to 0 C in an ice bath. Triethylphosphonoacetate (2.8 g, 2.5 mL, 2.0 equiv) was then added dropwise via syringe to the suspension of sodium hydride over 15 minutes, and the mixture was stirred for 30 min. The solution of corresponding ketone (6 mmol, 1.0 equiv) in THF (10 mL) was then added to the reaction flask via syringe at 0 C. The reaction mixture was allowed to warm to 60 C (detected by TLC analysis). The septum and the balloon were removed, and the reaction was carefully quenched by the slow addition of aqueous sat. NH4Cl solution. The mixture was then extracted with ethyl acetate (3×), washed with brine, dried with Na2SO4 , filtered, concentrated in vacuo and purified by silica gel chromatography to afford the corresponding alpha, beta-unsaturated ester.

Molecular Weight:182.60
XLogP3:2
Hydrogen Bond Acceptor Count:2
Exact Mass:182.0134572
Monoisotopic Mass:182.0134572
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:193
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes