aniline;hydrochloride

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

Procedure: 28 mL of POCl3 are added to 39 mL stirred, cooled N,N-dimethylformamide, followed by 16 g of p-cyanophenylacetic. After 1 hour, the reaction mixture is heated at 80-90° C. until carbon dioxide is no longer evolved, about 6 hours. The mixture is cooled to room temperature, mixed within 100 g of ice, and the aqueous mixture is shaken with a small amount of charcoal. The aqueous solution is made basic with potassium carbonate and extracted 3 times with 200 mL portions of dichloromethane. The combined organic layers are washed with distilled water, dried with sodium sulphate and evaporated to a dark oil. This oil is subjected to basic hydrolysis to produce the free dihaldehyde and at the same time convert the nitrile to the corresponding carboxylate. Thus, the oil is suspended in 100 mL of water and 25 mL of 50% aqueous NaOH are added with stirring. The mixture is heated at 70° C. until a homogenous aqueous solution results. The solution is neutralised with concentrated hydrochloric acid and 25 g of aniline hydrochloride dissolved in 100 mL of water are added. The yellow orange precipitate is collected on a fritted glass filter and dried in the oven at 50° C. is no longer evolved, about 6 hours extracted 3 times with 200 mL portions of dichloromethane The combined organic layers are washed with distilled water dried with sodium sulphate evaporated to a dark oil This oil is subjected to basic hydrolysis to produce the free dihaldehyde with stirring The mixture is heated at 70° C. until a homogenous aqueous solution results are added The yellow orange precipitate is collected on a fritted glass filter dried in the oven at 50° C.

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

Procedure: 2-(7,8-Dimethoxy-2H-1-benzopyran-5-ylmethyl)-3-morpholino acrylonitrile (562 g, 1.64 mol) and aniline hydrochloride (234 g, 1.80 mol) were refluxed in SD3A (2.4 L) for one hour. The reaction was cooled, and guanidine hydrochloride (313 g, 3.28 mol) and sodium methoxide (275 g, 5.08 mol) were added. After continued reflux, the product crystallized from the cooled reaction mixture. Filtration followed by water wash (2 L) gave 2,4-diamino-5-(7,8-dimethoxy-2H-1-benzopyran-5-ylmethyl)pyrimidine (220 g, 42.7%). Crystallization from ethanol-water gave title compound, mp 235°-238°, identical to the product of Example 1C. The reaction was cooled After continued reflux the product crystallized from the cooled reaction mixture Filtration wash (2 L)

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

Procedure: 2-(7,8-Dimethoxy-2H-1-benzopyran-5-ylmethyl)-3-morpholino acrylonitrile (562 g, 1.64 mol) and aniline hydrochloride (234 g, 1.80 mol) were refluxed in SD3A (2.4 L) for one hour. The reaction was cooled, and guanidine hydrochloride (313 g, 3.28 mol) and sodium methoxide (275 g, 5.08 mol) were added. After continued reflux, the product crystallized from the cooled reaction mixture. Filtration followed by water wash (2 L) gave 2,4-diamino-5-(7,8-dimethoxy-2H-1-benzopyran-5-ylmethyl)pyrimidine (220 g, 42.7%). Crystallization from ethanol-water gave title compound, mp 235°-238°, identical to the product of Example 1C. The reaction was cooled After continued reflux the product crystallized from the cooled reaction mixture Filtration wash (2 L)

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

Procedure: Fluorobenzenes have hitherto been prepared from the corresponding substituted anilines by diazotization and subsequent replacement of the diazo group by fluorine. Thus the preparation of fluorobenzene by diazotization of aniline hydrochloride, conversion of the resulting benzenediazonium chloride into the tetrafluoroborate and subsequent heating has long been known (G. Balz and G. Schiemann, Ber. 60 (1927) 1188; D. T. Flood, Org. Synth. Coll. Vol II (1943) 295). In addition, the preparation of fluorobenzene by diazotization of aniline in anhydrous hydrogen fluoride at 0° C. with subsequent decomposition of the resulting benzenediazonium fluoride at 20° C. is also described (Kirk-Othmer, Encyclopedia of Chemical Technology, 3rd ed. Vol. 10, p. 908). 1,3-Difluorobenzene could be obtained analogously in a 31% yield, relative to m-phenylenediamine as starting compound, by heating benzene-1,3-bis-diazonium tetrafluoroborate (G. Schiemann and R. Pillarsky, Ber. 62 (1929) 3035-3043, especially 3029). The diazotization of 3-fluoroaniline in anhydrous hydrogen fluoride in the presence of either ammonium fluoride or tertiary amines or dimethyl sulfoxide produced in each case 1,3-difluorobenzene in a yield of 46 to 73% (U.S. Pat. No. 4,075,252 and U.S. Pat. No. 4,096,196). subsequent heating

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

Procedure: Fluorobenzenes have hitherto been prepared from the corresponding substituted anilines by diazotization and subsequent replacement of the diazo group by fluorine. Thus the preparation of fluorobenzene by diazotization of aniline hydrochloride, conversion of the resulting benzenediazonium chloride into the tetrafluoroborate and subsequent heating has long been known (G. Balz and G. Schiemann, Ber. 60 (1927) 1188; D. T. Flood, Org. Synth. Coll. Vol II (1943) 295). In addition, the preparation of fluorobenzene by diazotization of aniline in anhydrous hydrogen fluoride at 0° C. with subsequent decomposition of the resulting benzenediazonium fluoride at 20° C. is also described (Kirk-Othmer, Encyclopedia of Chemical Technology, 3rd ed. Vol. 10, p. 908). 1,3-Difluorobenzene could be obtained analogously in a 31% yield, relative to m-phenylenediamine as starting compound, by heating benzene-1,3-bis-diazonium tetrafluoroborate (G. Schiemann and R. Pillarsky, Ber. 62 (1929) 3035-3043, especially 3029). The diazotization of 3-fluoroaniline in anhydrous hydrogen fluoride in the presence of either ammonium fluoride or tertiary amines or dimethyl sulfoxide produced in each case 1,3-difluorobenzene in a yield of 46 to 73% (U.S. Pat. No. 4,075,252 and U.S. Pat. No. 4,096,196). subsequent heating

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

Procedure: A mixture of 53.6 g (0.02 mole) of 3,8-dibutyl-2,7-dioxospiro-[4.4]nonane-1,6-dione, 10.32 g (0.08 mole) of aniline hydrochloride and 40 ml of aniline was placed in a 500 ml round bottom flask and heated to reflux. After refluxing for 6 hours, the aniline was removed by distillation at reduced pressure. The resulting mixture was subjected to column chromatography employing a 2:1 mixture of diethyl ether and petroleum ether as eluent. The product, 3,8-dibutyl-2,7-diphenyl-2,7-diazaspiro[4.4]nonane-1,6-dione, was isolated as a viscous oil in a yield of about 86%. The infrared, 13C-NMR and mass spectra of the product were consistent with this structure. was placed in a 500 ml round bottom flask heated to reflux After refluxing for 6 hours the aniline was removed by distillation at reduced pressure a 2:1 mixture of diethyl ether and petroleum ether as eluent

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100 mL single necked flask fitted with a magnetic stirrer and a reflux condenser was charged with a 10.0 g (32 mmol) of 3-pentadecylcyclohexanone, 8.4 g (65 mmol) aniline hydrochloride and 12.05 g (130 mmol) of aniline. The resulting mixture was refluxed at 140° C. for 10 hours under positive pressure of nitrogen. The reaction mixture was cooled to room temperature, diluted with dichloromethane, and washed with aqueous sodium hydroxide solution and water and dried over sodium sulfate. Solvent was distilled off and excess aniline removed under vacuum. The desired 1,1-bis(4-aminophenyl)-3-pentadecylcyclohexan was obtained in a yield of 5.4 g (35% of theoretical). M.p. 107° C. A 100 mL single necked flask fitted with a magnetic stirrer and a reflux condenser The reaction mixture was cooled to room temperature washed with aqueous sodium hydroxide solution and water dried over sodium sulfate Solvent was distilled off excess aniline removed under vacuum

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Ethynyl-1-cyclohexanol (1.242 g, 10 mmol), aniline (0.931 g, 10 mmol), Ru3(CO)12 (32.0 mg, 0.05 mmol) and aniline hydrochloride (0.259 g, 2.0 mmol) were placed in a 10 ml round-bottomed flask, and the mixture was stirred at 120° C. for 12 hours. After cooling, dichloromethane (3 mL) was added, and the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL). The organic layer was dried over sodium sulfate, and the solvent was distilled away, whereby 2-methyl-3H-indole-3-spiro-1′-cyclohexane (24 mg; 0.12 mmol; yield, 1.2%; purity, 95% or more) was obtained. After cooling the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL) The organic layer was dried over sodium sulfate the solvent was distilled away

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Ethynyl-1-cyclohexanol (1.242 g, 10 mmol), aniline (0.931 g, 10 mmol), Ru3(CO)12 (32.0 mg, 0.05 mmol) and aniline hydrochloride (0.259 g, 2.0 mmol) were placed in a 10 ml round-bottomed flask, and the mixture was stirred at 120° C. for 12 hours. After cooling, dichloromethane (3 mL) was added, and the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL). The organic layer was dried over sodium sulfate, and the solvent was distilled away, whereby 2-methyl-3H-indole-3-spiro-1′-cyclohexane (24 mg; 0.12 mmol; yield, 1.2%; purity, 95% or more) was obtained. After cooling the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL) The organic layer was dried over sodium sulfate the solvent was distilled away

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Pentine-3-ol (0.757 g, 9 mmol), aniline (0.559 g, 6 mmol), Ru3(CO)12 (16.0 mg, 0.025 mmol) and aniline hydrochloride (0.130 g, 1.0 mmol) were placed in a 10 ml round-bottomed flask, and the mixture was stirred at 140° C. for 7.5 hours. After cooling, dichloromethane (3 mL) was added, and the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL). The organic layer was dried over sodium sulfate, and the solvent was distilled away, whereby a 9.3:1 mixture of 2-ethyl-3-methyl indole and 3-ethyl-2-methyl indole (1.06 g; 6.67 mmol; yield, 95%) was obtained. After cooling the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL) The organic layer was dried over sodium sulfate the solvent was distilled away whereby a 9.3:1 mixture of 2-ethyl-3-methyl indole

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Octyne-3-ol (1.136 g, 9 mmol), aniline (0.559 g, 6 mmol), Ru3(CO)12 (16.0 mg, 0.025 mmol) and aniline hydrochloride (0.130 g, 1.0 mmol) were placed in a 10 ml round-bottomed flask, and the mixture was stirred at 140° C. for 9 hours. After cooling, diethyl ether (3 mL) was added, and the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL). The organic layer was dried over sodium sulfate, and the solvent was distilled away, whereby an 11:1 mixture of 3-methyl-2-pentyl indole and 2-methyl-3-pentyl indole (1.262 g; 6.3 mmol; yield, 95%; purity, about 95% or more) was obtained. After cooling the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL) The organic layer was dried over sodium sulfate the solvent was distilled away whereby an 11:1 mixture of 3-methyl-2-pentyl indole

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Octyne-3-ol (1.136 g, 9 mmol), aniline (0.559 g, 6 mmol), Ru3(CO)12 (16.0 mg, 0.025 mmol) and aniline hydrochloride (0.130 g, 1.0 mmol) were placed in a 10 ml round-bottomed flask, and the mixture was stirred at 140° C. for 9 hours. After cooling, diethyl ether (3 mL) was added, and the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL). The organic layer was dried over sodium sulfate, and the solvent was distilled away, whereby an 11:1 mixture of 3-methyl-2-pentyl indole and 2-methyl-3-pentyl indole (1.262 g; 6.3 mmol; yield, 95%; purity, about 95% or more) was obtained. After cooling the organic layer was washed twice with 1 M hydrochloric acid (2 mL) and once with water (2 mL) The organic layer was dried over sodium sulfate the solvent was distilled away whereby an 11:1 mixture of 3-methyl-2-pentyl indole