2-(2-chloroethoxy)benzaldehyde

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

Procedure: 40.0 g of 2- hydroxybenzaldehyde, 84 g of 1-chloro-2-tosyloxyethane and 50 g of potassium carbonate are added to 270 ml of dimethylformamide, and the mixture is stirred at room temperature for 3 days. After the reaction, half of the solvent is distilled off under reduced pressure. About 600 ml of water are added to the residue, and the mixture is extracted with ether. The extract is washed with 10% sodium hydroxide solution and water, dried and then distilled to remove the solvent. The residue is distilled at 116°-118° C./0.2-0.3 mmHg to give 2-(2-chloroethyloxy)benzaldehyde (51.9 g, yield: 86%) as a coloress oil. The properties of this compound are the same as those disclosed in J.O.C., 18, 1380-1402 (1953). After the reaction, half of the solvent is distilled off under reduced pressure About 600 ml of water are added to the residue the mixture is extracted with ether The extract is washed with 10% sodium hydroxide solution and water dried distilled to remove the solvent The residue is distilled at 116°-118° C./0.2-0.3 mmHg

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

Procedure: 40.0 g of 2- hydroxybenzaldehyde, 84 g of 1-chloro-2-tosyloxyethane and 50 g of potassium carbonate are added to 270 ml of dimethylformamide, and the mixture is stirred at room temperature for 3 days. After the reaction, half of the solvent is distilled off under reduced pressure. About 600 ml of water are added to the residue, and the mixture is extracted with ether. The extract is washed with 10% sodium hydroxide solution and water, dried and then distilled to remove the solvent. The residue is distilled at 116°-118° C./0.2-0.3 mmHg to give 2-(2-chloroethyloxy)benzaldehyde (51.9 g, yield: 86%) as a coloress oil. The properties of this compound are the same as those disclosed in J.O.C., 18, 1380-1402 (1953). After the reaction, half of the solvent is distilled off under reduced pressure About 600 ml of water are added to the residue the mixture is extracted with ether The extract is washed with 10% sodium hydroxide solution and water dried distilled to remove the solvent The residue is distilled at 116°-118° C./0.2-0.3 mmHg

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

Procedure: A solution of 2-(2-chloroethoxy)benzaldehyde (40; 2.5 g, 13.5 mmol), pyrrolidine (172; 1.9 g, 26.8 mmol), K2CO3 (3.8 g, 27.2 mmol) and NaI (0.6 g, 4.2 mmol) in DMF (50 mL) was stirred at 80° C. for 12 h. Water (200 mL) was added and the mixture was extracted with ethyl acetate (3×150 mL). The combined organic layers were washed brine (3×50 mL), dried (Na2SO4) and concentrated under reduced pressure. The resulting residue was purified by chromatography (dichloromethane:methanol=100:1) to give 2-(2-(pyrrolidin-1-yl)ethoxy)benzaldehyde 41 (1.63 g, 7.43 mmol, 55%) as a pale yellow solid. the mixture was extracted with ethyl acetate (3×150 mL) The combined organic layers were washed brine (3×50 mL) dried (Na2SO4) concentrated under reduced pressure The resulting residue was purified by chromatography (dichloromethane:methanol=100:1)

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloroethyl 4-methylbenzenesulfonate (39; 27.0 g, 0.115 mol), 2-hydroxybenzaldehyde (25; 14.0 g, 0.115 mol) and K2CO3 (31.7 g, 0.23 mol) in DMF (100 mL) was stirred at 45° C. for 12 h. Water (200 mL) was added and the mixture was extracted with ethyl acetate (3×150 mL). The combined organic layers were washed saturated brine (3×50 mL), dried (Na2SO4) and concentrated under reduced pressure. The resulting residue was purified by chromatography (petroleum ether:ethyl acetate=10:1) to give 2-(2-chloroethoxy)benzaldehyde 40 (16.8 g, 0.091 mol, 79%) as a pale yellow solid. the mixture was extracted with ethyl acetate (3×150 mL) The combined organic layers were washed saturated brine (3×50 mL) dried (Na2SO4) concentrated under reduced pressure The resulting residue was purified by chromatography (petroleum ether:ethyl acetate=10:1)

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

Procedure: To a solution of 46.5 g of 2-(2-chloroethyloxy)benzaldehyde and 33.2 g of ethylene glycol in 500 ml of benzene in added 0.5 ml of 85% phosphoric acid, and the mixture is refluxed with stirring for about 18 hours while removing the produced water. After the reaction, the reaction mixture is cooled with ice and is made alkaline with saturated sodium bicarbonate solution to separate into two layers. The benzene layer is taken, washed with saturated saline solution, dried and then distilled to remove the solvent. The crude product thus obtained is distilled to give 56 g of 2-(2-chloroethyloxy)benzaldehyde ethyleneacetal (yield: 97%) as a colorless oil. b.p. 130°-135° C./0.3 mmHg. while removing the produced water After the reaction the reaction mixture is cooled with ice to separate into two layers washed with saturated saline solution dried distilled to remove the solvent The crude product thus obtained is distilled

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

Procedure: 40.0 g of 2-hydroxybenzaldehyde, 84 g of 1-chloro-2-tosyloxyethane and 50 g of potassium carbonate are added to 270 ml of dimethylformamide, and the mixture is stirred at room temperature for 3 days. After the reaction, half of the solvent is removed under reduced pressure. About 600 ml of water are added to the residue, and the mixture is extracted with ether. The extract is washed with 10% sodium hydroxide solution and water, dried and then concentrated under reduced pressure to remove solvent. The residue is distilled at 116°-118° C./0.2-0.3 mmHg to give 2-(2-chloroethyloxy)benzaldehyde (51.9 g, yield: 86%) as a colorless oil. The properties of this compound are the same as those disclosed in J.O.C., 18, 1380-1402 (1953). After the reaction, half of the solvent is removed under reduced pressure About 600 ml of water are added to the residue the mixture is extracted with ether The extract is washed with 10% sodium hydroxide solution and water dried concentrated under reduced pressure to remove solvent The residue is distilled at 116°-118° C./0.2-0.3 mmHg

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

Procedure: 40.0 g of 2- hydroxybenzaldehyde, 84 g of 1-chloro-2-tosyloxyethane and 50 g of potassium carbonate are added to 270 ml of dimethylformamide, and the mixture is stirred at room temperature for 3 days. After the reaction, half of the solvent is distilled off under reduced pressure. About 600 ml of water are added to the residue, and the mixture is extracted with ether. The extract is washed with 10% sodium hydroxide solution and water, dried and then distilled to remove the solvent. The residue is distilled at 116°-118° C./0.2-0.3 mmHg to give 2-(2-chloroethyloxy)benzaldehyde (51.9 g, yield: 86%) as a coloress oil. The properties of this compound are the same as those disclosed in J.O.C., 18, 1380-1402 (1953). After the reaction, half of the solvent is distilled off under reduced pressure About 600 ml of water are added to the residue the mixture is extracted with ether The extract is washed with 10% sodium hydroxide solution and water dried distilled to remove the solvent The residue is distilled at 116°-118° C./0.2-0.3 mmHg