N-hydroxybenzenecarboximidoyl chloride

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: A solution of chlorine (1.5 g) in carbon tetrachloride (42 ml) was added in portions in a stirred partial solution of benzaldehyde oxime [2.5 g; 1H NMR: δ8.18 (1H, s), 9.40 (1H, brs) ppm] in carbon tetrachloride (20 ml) at room temperature. Following the addition, the reaction mixture was stirred at room temperature for 3 hours then poured into water. The organic layer was separated, dried and concentrated to give almost pure α-chlorobenzaldehyde oxime (3.2 g) as a yellow liquid. A solution of sodium methanethiolate (0.68 g) in methanol (15 ml) was added dropwise to an ice-cooled and stirred solution of part of this α-chlorobenzaldehyde oxime (1.5 g) in methanol (15 ml). Following the addition, the reaction mixture was stirred for 2 hours with continued cooling in iced-water. The methanol was removed under reduced pressure and the residue was chromatographed using dichloromethane as eluant to give a single stereoisomer of α-methylthiobenzaldehyde oxime (0.67 g, 42% yield) as a white crystalline solid, m.p. 76°-78° C., 1H, NMR: δ2.08 (3H, s), 9.12 (1H, s) ppm. the addition The organic layer was separated dried concentrated

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

Procedure: A round bottom flask was charged with a solution of 20 g of K2CO3 in 50 mL of water and cooled in an ice bath. Cyclopentylidene-hydrazine (7.9 g, 80 mmol) in 25 mL of CH2Cl2 was added, followed by a drop-wise addition of benzohydroximoyl chloride (5 g, 0.032 mmol) in 25 mL of CH2Cl2 over a period of 15 minutes. The mixture was stirred for several days, and allowed to warm to room temperature. Water (50 mL) and CH2Cl2 (50 mL) were added and the phases were separated. The organic layer was washed twice with 50 mL of water, dried over MgSO4, and filtered. The solvent was removed in vacuo, leaving 9 g of a waxy solid. Crystallization from ethyl acetate/hexane provided 3.5 g (50%) of 3-phenyl-1-oxa-2,4-diaza-spiro[4.4]non-2-en-4-ylamine after drying. 1H-NMR (300 MHz, CDCl3) δ (ppm): 7.72 ((m, 2H), 7.46 (m, 3H), 3.54 (s, 2H), 2.1 (m, 2H), 2.0 (m, 2H), 1.85 (m, 2H), 1.8 (m, 2H). cooled in an ice bath the phases were separated The organic layer was washed twice with 50 mL of water dried over MgSO4 filtered The solvent was removed in vacuo leaving 9 g of a waxy solid Crystallization from ethyl acetate/hexane

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of isopropylidene-hydrazine (0.59 g, 8 mmol) in 15 mL of chloroform and an aqueous solution of K2CO3 (0.5 g in 3 mL of water) were mixed and cooled in a 50 mL round-bottom flask chilled with ice water. A solution of benzohydroximoyl chloride (0.51 g, 3.2 mmol) in 10 mL of chloroform was added slowly with vigorous magnetic stirring. The ice batch was replaced with a 40° C. water bath and the mixture was stirred at 40° C. for 2 hours and then monitored by TLC (1:1 ethyl acetate:hexanes). When progression of the reaction began to significantly decelerate, the mixture was worked up by the addition of 10 mL of water and 60 mL of chloroform or methylene chloride. The organic layer was removed in a separatory funnel, dried over MgSO4, and the solvent removed on a rotary evaporator to yield a semi-solid. The crude product was triturated with 2% ether in hexanes (30 mL), by magnetic stirring in a round bottom flask or manipulating the material with a spatula. Filtration and air-drying provided 5,5-dimethyl-3-phenyl-[1,2,4]oxadiazol-4-ylamine in ca. 40% yield. 1H-NMR (300 MHz, CDCl3) δ (ppm): 7.77 (m, 2H), 7.48 (m, 3H), 3.4 (br), 1.55 (s, 6H). cooled in a 50 mL round-bottom flask was replaced with a 40° C. The organic layer was removed in a separatory funnel dried over MgSO4 the solvent removed on a rotary evaporator to yield a semi-solid The crude product was triturated with 2% ether in hexanes (30 mL) by magnetic stirring in a round bottom flask Filtration air-drying

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

Procedure: 60.5 g (0.5 mol) of benzaldoxime was suspended in 390 ml of 8N hydrochloric acid and chlorine gas was bubbled into the suspension while stirring and maintaining the reaction temperature at from 5° to 15° C. The oxime immediately showed a green color upon reaction with chlorine and, after allowing the reaction mixture to stand, pale yellow crystals of α-chlorobenzaldoxime precipitated. Filtration of the reaction mixture yielded 66 g of crystals having a melting point of 45°-47° C. Yield, about 84%. chlorine gas was bubbled into the suspension maintaining the reaction temperature at from 5° to 15° C upon reaction with chlorine pale yellow crystals of α-chlorobenzaldoxime precipitated Filtration of the reaction mixture

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To N-hydroxybenzenecarboximidoyl chloride (622 mg, 4 mmol) in dry DCM (6 ml) was added 5-hexyn-1-ol (431 mg, 4.4 mmol). The mixture was cooled to 0° C. under nitrogen as triethylamine (0.612 ml, 4.4 mmol) was added dropwise over 10 min. Stirred for a further 20 min at 0° C. then at room temperature overnight. The mixture was washed with water and the organic phase evaporated. The product was purified by silica SPE (20 g) eluting with EtOAc-cyclohexane (1:2, then 3:1) to give a white waxy solid (443 mg). was added dropwise over 10 min at room temperature overnight The mixture was washed with water the organic phase evaporated The product was purified by silica SPE (20 g) eluting with EtOAc-cyclohexane (1:2

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

Procedure: Triethylamine (7.28 ml) was added to a solution of α-chlorobenzaldehyde oxime (4.04 g) and 2-propyn-1-ol (1.66 ml) in tetrahydrofuran (130 ml) and stirred at room temperature for 4 days. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The remaining crystals were recrystallized from ethyl acetate-hexane to obtain (3-phenyl-5-isoxazolyl)methanol (3.42 g, yield 75%) as colorless crystals. m.p. 48-49° C. extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated The remaining crystals were recrystallized from ethyl acetate-hexane

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

Procedure: Triethylamine (7.28 ml) was added to a solution of α-chlorobenzaldehyde oxime (4.04 g) and 2-propyn-1-ol (1.66 ml) in tetrahydrofuran (130 ml) and stirred at room temperature for 4 days. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The remaining crystals were recrystallized from ethyl acetate-hexane to obtain (3-phenyl-5-isoxazolyl)methanol (3.42 g, yield 75%) as colorless crystals. m.p. 48-49° C. extracted with ethyl acetate The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride dried (MgSO4) concentrated The remaining crystals were recrystallized from ethyl acetate-hexane

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

Procedure: A round bottom flask was charged with a solution of 20 g of K2CO3 in 50 mL of water and cooled in an ice bath. Cyclopentylidene-hydrazine (7.9 g, 80 mmol) in 25 mL of CH2Cl2 was added, followed by a drop-wise addition of benzohydroximoyl chloride (5 g, 0.032 mmol) in 25 mL of CH2Cl2 over a period of 15 minutes. The mixture was stirred for several days, and allowed to warm to room temperature. Water (50 mL) and CH2Cl2 (50 mL) were added and the phases were separated. The organic layer was washed twice with 50 mL of water, dried over MgSO4, and filtered. The solvent was removed in vacuo, leaving 9 g of a waxy solid. Crystallization from ethyl acetate/hexane provided 3.5 g (50%) of 3-phenyl-1-oxa-2,4-diaza-spiro[4.4]non-2-en4-ylamine after drying. 1H-NMR (300 MHz, CDCl3)δ(ppm): 7.72 ((m, 2H), 7.46 (m, 3H), 3.54 (s, 2H), 2.1 (m, 2H), 1.85 (m, 2H), 1.8 (m., 2H). cooled in an ice bath the phases were separated The organic layer was washed twice with 50 mL of water dried over MgSO4 filtered The solvent was removed in vacuo leaving 9 g of a waxy solid Crystallization from ethyl acetate/hexane

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of isopropylidene-hydrazine (0.59 g, 8 mmol) in 15 mL of chloroform and an aqueous solution of K2CO3 (0.5 g in 3 mL of water) were mixed and cooled in a 50 mL round-bottom flask chilled with ice water. A solution of benzohydroximoyl chloride (0.51 g, 3.2 mmol) in 10 mL of chloroform was added slowly with vigorous magnetic stirring. The ice batch was replaced with a 40° C. water bath and the mixture was stirred at 40° C. for 2 hours and then monitored by TLC (1:1 ethyl acetate:hexanes). When progression of the reaction began to significantly decelerate, the mixture was worked up by the addition of 10 mL of water and 60 mL of chloroform or methylene chloride. The organic layer was removed in a separatory funnel, dried over MgSO4, and the solvent removed on a rotary evaporator to yield a semi-solid. The crude product was triturated with 2% ether in hexanes (30 mL), by magnetic stirring in a round bottom flask or manipulating the material with a spatula. Filtration and air-drying provided 5,5-dimethyl-3-phenyl-[1,2,4]oxadiazol-4-ylamine in ca. 40% yield. 1H-NMR (300 MHz, CDCl3)δ(ppm): 7.77 (m, 2H), 7.48 (m, 3H), 3.4 (br), 1.55 (s, 6H). cooled in a 50 mL round-bottom flask was replaced with a 40° C. The organic layer was removed in a separatory funnel dried over MgSO4 the solvent removed on a rotary evaporator to yield a semi-solid The crude product was triturated with 2% ether in hexanes (30 mL) by magnetic stirring in a round bottom flask Filtration air-drying