2,2,2-trichloroethane-1,1-diol

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: To a stirred solution of sodium sulfate (58.5 g, 412 mmol) in water (100 mL) was added a solution of chloralhydrate (9.36 g, 56.6 mmol) in water (120 mL). Chloroanisidine 39d (10 g, 51.5 mmol) was added followed by 37% HCl (20 mL). A solution of hydroxylamine (50% in water, 4.7 mL, 154.5 mmol) in 50 mL was then added and the reaction mixture was refluxed for 90 min. The suspended solid was filtered off, and washed with water and ether. Organics were dried over Na2SO4, filtered, and concentrated under reduced pressure to yield compound 102d as a brown solid. the reaction mixture was refluxed for 90 min The suspended solid was filtered off washed with water and ether Organics were dried over Na2SO4 filtered concentrated under reduced pressure

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

Procedure: Reaction of 3,4-difluoroaniline with chloral hydrate and hydroxylamine followed cyclization with sulfuric acid, in a manner analogous to Parts A and B of Preparation 3, gave 5,6-difluoroisatin, which was reacted with hydrazine hydrate followed by sodium methoxide in ethanol, in a manner analogous to Preparation 1, to give the title compound, m.p. 187°-190° C. in a manner analogous to Parts A and B of Preparation 3

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

Procedure: 3,4-Dimethylaniline was converted into 3,4-dimethylisonitrosoacetanilide by reaction with chloral hydrate and hydroxylamine, using the method described in "Organic Syntheses," Collective Volume I, page 327. The 3,4-dimethyl-isonitrosoacetanilide was cyclized with sulfuric acid, according to the method of Baker et al., Journal of Organic Chemistry, 17, 149 (1952), to give 4,5-dimethylisatin (m.p. 225°-226° C.) and 5,6-dimethylisatin (m.p. 217°-218° C.).

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

Procedure: To a stirred solution of sodium sulfate (58.5 g, 412 mmol) in water (100 mL) was added a solution of chloralhydrate (9.36 g, 56.6 mmol) in water (120 mL). Chloroanisidine 215d (10 g, 51.5 mmol) was added followed by 37% HCl (20 mL). A solution of hydroxylamine (50% in water, 4.7 mL, 154.5 mmol) in 50 mL was then added and the reaction mixture was refluxed for 90 min. The suspended solid was filtered off, and washed with water and ether. Organics were dried over Na2SO4, filtered, and concentrated under reduced pressure to yield compound 245d as a brown solid. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 3.86 (s, 3H), 6.98 (d, J=8.07 Hz, 1H), 7.31 (t, J=8.07 Hz, 1H), 7.61 (d, J=8.07 Hz, 1H), 7.66 (s, 1H), 9.43 (s, 1H), 12.43 (s, 1H). the reaction mixture was refluxed for 90 min The suspended solid was filtered off washed with water and ether Organics were dried over Na2SO4 filtered concentrated under reduced pressure

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 5 l flask is placed chloral hydrate (90 g, 0.54 mole) and water (1200 ml). To this solution is added sodium sulfate decahydrate (1300 g, 10.9 mole) followed by a solution of o-methylaniline (54 g, 0.5 mole) in water (300 ml) containing concentrated hydrochloric acid (43 ml, 0.5 mole). Then a solution of hydroxylamine hydrochloride (110 g, 1.58 mole) in water (50 ml) is added. The reaction mixture is heated to reflux over a 90 minute period and refluxed 30 minutes. The reaction is cooled in ice and the resulting crystalline ortho-isonitrosoacetotoluidide is isolated by filtration and air dried. The orthoisonitrosoacetotoluidide is dissolved in portions in concentrated sulfuric acid (325 ml) that is preheated to 50° C. with vigorous stirring. The reaction temperature is maintained under 75° C. When the addition is complete, the mixture is heated at 80° C. for 30 minutes, cooled, and poured unto ice (3 kg). The 7-methylisatin is isolated by filtration. The 7-methylisatin is purified by dissolution in dilute sodium hydroxide. The basic solution is treated with 4N hydrochloric acid until a slight amount of precipitation is evident. The mixture is filtered and the filtrate is acidified. The pure 7-methylisatin is recovered by filtration and dried in vacuo at 80° C. and 0.1 mm pressure, mp 114°-145° C. (A. Wahl, et al., Ann. Chim. 5 314 (1926). In a 5 l flask is placed The reaction mixture is heated to reflux over a 90 minute period refluxed 30 minutes The reaction is cooled in ice the resulting crystalline ortho-isonitrosoacetotoluidide is isolated by filtration and air dried The orthoisonitrosoacetotoluidide is dissolved in portions in concentrated sulfuric acid (325 ml) that is preheated to 50° C. with vigorous stirring When the addition the mixture is heated at 80° C. for 30 minutes cooled poured unto ice (3 kg)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of chloral hydrate (59.3 g, 0.36 mol), water (700 ml), and sodium sulphate (85.8 g, 0.60 mol), was heated to 50° C. When 50° C. was reached, sequentially a mixture of 3-ethyl-aniline (40.8 g, 0.33 mol), water (700 ml) and conc. hydrochloric acid (33.6 ml) and a mixture of hydroxylamine hydrochloride (74.8 g, 1.04 mol) and water (330 ml) were added. The resulting mixture was heated to 80° C. during 30 minutes and kept for another 10 minutes at this temperature before the reaction mixture was cooled on an ice-bath. The resulting precipitate was filtered off, washed with water and dried in vacuum over P2O5 to give an isonitrosoacetanilide (36.6 g), yield 58%. The isonitrosoacetanilide (10.0 g, 0.05 mol), was added portionwise to a mixture of water (9 ml) and conc. sulphuric acid (60 ml) prewarmed to 50° C., maintaining the temperature between 50-55° C. When the addition was completed, the mixture was heated to 80° C. and kept at this temperature for 10 minutes. The reaction mixture was then cooled on an ice-bath and poured on 10-12 times the reaction volume of crushed ice. The mixture was then left standing for about one hour. The water suspension was extracted with dichloromethane which was dried and evaporated resulting in an mixture of the two analogues 4-ethyl and 6-ethyl isatins approximately 0.68:1 (7.6 g), yield 84%. When 50° C. were added The resulting mixture was heated to 80° C. during 30 minutes was cooled on an ice-bath The resulting precipitate was filtered off washed with water dried in vacuum over P2O5

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloral hydrate (9.6 g) was dissolved in 200 mL of water containing 83 g of sodium sulfate. The solution was warmed to 60° C., a solution of 11.4 g of hydroxylamine hydrochloride in 50 mL of water was added and the mixture was held at 60° C. In a separate flask, 6.4 g of 4-anisidine and 4.3 mL of concentrated hydrochloric acid in 80 mL of water was warmed to 80° C. The first solution was added to the second and the mixture refluxed for 2 minutes after which it was cooled slowly to room temperature and then cooled in an ice bath. The tan precipitate was collected by vacuum filtration, washed with water and dried under vacuum to give 8.6 g (85% yield) of N-(2-hydroximinoacetyl)anisidine. was held at 60° C The first solution was added to the second and the mixture refluxed for 2 minutes after which it was cooled slowly to room temperature cooled in an ice bath The tan precipitate was collected by vacuum filtration washed with water dried under vacuum

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

Procedure: Depressants, for example, nonbarbiturates (e.g. bromides, chloral hydrate etc.), methaqualone, barbiturates, diazepam, flurazepam, phencyclidine, and fluoxetine;