Sodium amide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Chloro-4-cyclohexylacetophenone (0.25 moles) and phosphorus pentachloride (0.31 moles) are placed in a 3-necked flask equipped with a mechanical stirrer, a condenser connected to a nitrogen inlet, and a thermometer. The mixture is stirred at 33°-35° C. for 3 days. The cooled reaction mixture is poured onto 800 g. of ice and extracted with 3×500 ml. of ether. The ether fraction is washed with 2×100 ml water 4×100 ml of 5% sodium hydroxide, 3×=ml water, 2×50 ml of saturated saline and dried over sodium sulfate. The ether is removed to give the chlorinated intermediate. The intermediate is dissolved in anhydrous THF (200 ml) and is added dropwise to a freshly prepared solution of sodamide in liquid ammonia, using a dry-ice condenser. The reaction mixture is allowed to stir at room temperature overnight; then, it is poured into 50 ml of water and 500 ml of ether. The ether fraction is washed with 3×50 ml water and 50 ml of saturated saline and is dried over sodium sulfate. Removal of solvent gives a residue which is distilled to give 3-chloro-4-cyclohexylethynylbenzene. equipped with a mechanical stirrer, a condenser connected to a nitrogen inlet The cooled reaction mixture is poured onto 800 g of ice and extracted with 3×500 ml The ether fraction is washed with 2×100 ml water 4×100 ml of 5% sodium hydroxide, 3×=ml water, 2×50 ml of saturated saline dried over sodium sulfate The ether is removed to give the chlorinated intermediate to stir at room temperature overnight The ether fraction is washed with 3×50 ml water and 50 ml of saturated saline is dried over sodium sulfate Removal of solvent gives a residue which is distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 14.6 g. of 4-amino-3,5-dimethyl-α-[(methylsulfonyl)-methyl]-benzyl alcohol in 50 ml. of absolute dimethylsulfoxide was treated with 1.17 g. of sodium amide, stirred for 2 hours at room temperature, diluted with 500 ml. of water and extracted with two 500 ml. portions of ethyl acetate. The ethyl acetate extract was washed with two 200 ml. portions of water and evaporated under vacuum. After recrystallization of the residue from cyclohexane, there was obtained 4-amino-3,5-dimethyl-benzaldehyde having a melting point of 75°-76° C. diluted with 500 ml of water and extracted with two 500 ml The ethyl acetate extract was washed with two 200 ml portions of water and evaporated under vacuum After recrystallization of the residue from cyclohexane

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 6 mL THF solution of 1-(benzyloxy)-4-bromobenzene (500 mg, 1900 μmol) (commercially available from Sigma-Aldrich, St. Louis, Mo., USA) and ketene dimethyl acetal (359 μL, 3800 μmol) (commercially available from Sigma-Aldrich, St. Louis, Mo., USA) was added neat sodium amide (107 μL, 3800 μmol) (commercially available from Sigma-Aldrich, St. Louis, Mo., USA). The resulting mixture was heated to 80° C. and stirred for 48 hours. After the reaction was complete, it was quenched by slow addition of water. The resulting mixture was then extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. Solvent was removed in the presence of silica gel, and the residue was purified by column chromatography with 20% EtOAc/hexane to afford desired product H7.1 (274 mg, yield, 60%). MS ESI (pos.) m/e: 271.1 (M+H)+. it was quenched by slow addition of water The resulting mixture was then extracted with EtOAc The organic layer was washed with brine dried over MgSO4 Solvent was removed in the presence of silica gel the residue was purified by column chromatography with 20% EtOAc/hexane

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 8.0 g of 7-methoxyisoquinoline in 45 ml of N,N-dimethylaniline was warmed at 60° C., and then 5.9 g of sodium amide was added. The reaction mixture was heated at 130° C. over a period of 2 hours, and stirred for further 1 hour under the same conditions. After being cooled, the reaction mixture was poured into ice water and extracted with chloroform. The extract was washed with water, and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel and recrystallized from benzene to give 5.7 g of the title compound as colorless flakes. After being cooled extracted with chloroform The extract was washed with water dried over anhydrous magnesium sulfate The drying agent was removed by filtration the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel recrystallized from benzene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 32.1 g (0.25 mol) of o-chlorophenol were slowly added dropwise under nitrogen to a mixture of 20.5 g (0.5 mol) of 95% by weight pure crystalline sodium amide and 750 ml of diethylamine. The reaction mixture was refluxed under nitrogen for 72 h with stirring. The workup comprised hydrolysis with 100 ml of saturated aqueous ammonium chloride solution, distillative removal of excess diethylamine, neutralization with dilute hydrochloric acid up to a pH of 7.5, extraction of the residue with a total of 600 ml of methylene chloride, drying over sodium sulfate and concentrating of the organic phase. Thereafter the crude oil thus obtained (46.3 g) was distilled, which yielded 31.5 g (76%) of 3-diethylaminophenol (purity>96% (GC)). The reaction mixture was refluxed under nitrogen for 72 h hydrolysis with 100 ml of saturated aqueous ammonium chloride solution, distillative removal of excess diethylamine, neutralization with dilute hydrochloric acid up to a pH of 7.5, extraction of the residue with a total of 600 ml of methylene chloride drying over sodium sulfate concentrating of the organic phase Thereafter the crude oil thus obtained (46.3 g) was distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of (methoxymethyl)triphenylphosphonium chloride and sodamide (0.4 g of a 1:1 molar mixture) in dry THF was added a solution of methyl 2-(3-benzyl-2-thienyl)-2-oxoacetate (220 mg, 0.8 mmol) in dry THF (5 ml). The reaction mixture was stirred at room temperature for 30 minutes. More (methoxymethyl)triphenylphosphonium chloride and sodamide (0.2 g of a 1:1 molar mixture) were added and stirring was continued for a further one hour. The reaction mixture was poured into water and then extracted with ether. The combined ether layers were washed with water and brine and then dried. Filtration through a pad of silica gel to remove triphenylphosphine oxide, followed by HPLC (eluent dichloromethane) afforded (Z)-methyl 2-(3-benzyl-2-thienyl)-3-methoxypropenoate, an oil (100mg), 1H nmr : delta 3.64 (3H, s), 3.78 (6H,s), 6.75 (1H,d), 7.0-7.4 (6H,m), 7.60 (1H,s) ppm; and (E)-methyl 2-(3-benzyl-2-thienyl)-3-methoxypropenoate, an oil (30 mg), 1H nmr : delta 3.64 (3H,s), 3.80 (3H,s), 3.82 (3H,s), 6.56 (1H,s), 6.75 (1H,d}, 7.0-7.3 (6H,m}ppm. stirring was continued for a further one hour extracted with ether The combined ether layers were washed with water and brine dried Filtration through a pad of silica gel to remove triphenylphosphine oxide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,3-Lutidine (321 g) was added with stirring to a solution of sodamide (351 g) in liquid ammonia (3 1). 1-Amino-3-chloropropane hydrochloride (429g) was added to this mixture over 8 minutes with stirring. Any liquid ammonia lost through evaporation was replaced. After 2 hours the reaction was quenched by the addition of ammonium chloride (120 g) and the reaction mixture was left to stand overnight to allow substantially complete escape of ammonia through evaporation. The residue so obtained was diluted with water (2 1) and extracted with dichloromethane. The extracts were dried (Na2SO4), the dichloromethane removed by evaporation and the residue distilled in vacuo to give 4-(3-methyl-2-pyridyl) butylamine (306.6 g). Any liquid ammonia lost through evaporation After 2 hours the reaction was quenched by the addition of ammonium chloride (120 g) the reaction mixture was left through evaporation The residue so obtained extracted with dichloromethane The extracts were dried (Na2SO4) the dichloromethane removed by evaporation the residue distilled in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Liquid ammonia (150 ml) was introduced into a 250 ml three-necked round bottomed flask equipped with a mechanical stirrer, dropping funnel and outlet tube and immersed in a dry ice/ethanol bath. Sodium amide was generated by addition of 20 mg of iron nitrate (Fe3+) followed by metallic sodium (2.09 g, 0.09 mol). The deep blue solution was stirred for one hour and a solution of collidine (1) (10.06 g, 0.083 mol) in 20 ml of dry diethylether was introduced into the reaction by addition over a period of 15 min. The resultant yellow suspension was stirred for an additional 45 min, followed by the addition or benzylchloride (6.33 g, 0.05 mol) dissolvedin 10 ml of dry diethylether. The reaction mixture was stirred for 45 min and excess sodium amide was neutralized by addition of ammonium chloride (4.82 g, 0.09 mol) dissolved in 20 ml of H2O. Ammonia was evaporated and the residue was partitioned between water and diethylether. The collected etheral phase was dried over sodium sulfate and evaporated. The brown residual oil was fractionated, and a fraction distilling at 130° C./0.1 mmHg was colelcted. equipped with a mechanical stirrer immersed in a dry ice/ethanol bath The resultant yellow suspension was stirred for an additional 45 min The reaction mixture was stirred for 45 min Ammonia was evaporated the residue was partitioned between water and diethylether The collected etheral phase was dried over sodium sulfate evaporated a fraction distilling at 130° C./0.1 mmHg

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: to 85.6 g (2.2 moles) of sodium amide in 1.5 liter of dry toluene was added 202 g (2 moles) of 1-methyl-3-pyrrolidinol so as not to exceed a temperature of 50° C. The mixture was then heated to 70° C. for 4.5 hours. The mixture was cooled and 381 g (2 moles) of o-toluenesulfonylchloride was added at a rapid drop while maintaining a temperature of 20°-30° C. with an ice bath. The mixture was stirred at room temperature for 2.5 hours and washed with water. The toluene solution was dried with sodium sulfate and concentrated. The residue, dissolved in 500 ml of dimethylformamide, was added to a reaction mixture prepared by adding 119 g (2.2 moles) of sodium methoxide and 274 g (2.0 moles) of salicylamide to one liter of dimethylformamide and the mixture was worked up as in preparation 1. Yield of product was 170 g (38%), m.p. 116°-118° C. a temperature of 50° C The mixture was cooled while maintaining a temperature of 20°-30° C. with an ice bath washed with water The toluene solution was dried with sodium sulfate concentrated The residue, dissolved in 500 ml of dimethylformamide was added to a reaction mixture prepared the mixture was worked up as in preparation 1

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-phenyl-6-methyl pyridine (0.815 g, 4.82 mmol), and sodium amide (752 mg, 19.3 mmol) in diethylaniline (10 mL) was heated at 180° C. for 72 hours. The reaction was cooled and quenched with ice (100 g), and the mixture extracted with EtOAc. The organic extract was washed with brine (50 mL), dried (MgSO4), silica gel (100 g) was added and the solvent evaporated in vacuo. The reaction was cooled quenched with ice (100 g) the mixture extracted with EtOAc The organic extract was washed with brine (50 mL) dried (MgSO4), silica gel (100 g) was added the solvent evaporated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Chloro-3-aminopyridine was alkylated with diethyl iodomethylphosphonate, sodium amide as base, with known methods. The obtained 6-chloro-3-pyridinylamino-methylphosphonic acid diethylester (0.5 mol) and N-bromosuccinimid (0.5 mol) in anhydrous carbontetrachloride is irradiated 2 hours with a 200 W lamp. The solid is filtered off, washed with carbontetrachloride and the solution is concentrated in vacuo. The obtained 6-chloro-3-pyridinylamino(bromomethyl)-phosphonic acid diethylester (0.1 mol) is warmed in tetrahydrofuran with triethylphosphite (0.1 mol) in 50° C. for 4 hours. The reaction mixture is concentrated in vacuo. The product is purified chromatographically (eluent dichloromethane: methanol 9:1). Yield 5.1 g. The solid is filtered off washed with carbontetrachloride the solution is concentrated in vacuo The reaction mixture is concentrated in vacuo The product is purified chromatographically (eluent dichloromethane: methanol 9:1)

反応条件: temp:190.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 105.8 g (2.71 moles) of sodamide and 332 g of xylene containing 1.0 cc of oleic acid was placed in a liter Magne Drive, equipped as described in Example 15. The autoclave was closed and purged of air with nitrogen and pressurized to 100 psig with nitrogen. The pressure relief valve was set at 100 psig. Cooling water was turned on the reflux condenser. The mixture was heated with stirring to 190° C. and 235.0 g (1.58 moles) of 2-(3-pentyl)pyridine was started adding from a Fisher-porter pressure bottle. The addition required 5.5 hours at 190° C.-215° C. The reaction mixture was heated an additional 5 hours within that temperature range until hydrogen almost stopped passing through the relief valve. The autoclave was cooled to 50° C., vented to atmospheric pressure and hydrolyzed with 200 cc of water. The oil layer was separated and distilled under vacuum to give 258.6 g of 2 -amino-6-(3-pentyl)pyridine. b.p. 163° C. at 60 mm. n25D 1.5357 (yield 68.1%). This 2-amino-6-pentyl)pyridine is a new composition of matter. It is a novel liquid aminopyridine and has valuable biocidal properties. When this amination is repeated at atmospheric pressure under classic Chichibabin conditions, the product is 6,6'-di-(3-pentyl)-2,2'-bipyridyl as shown in McGill, U.S. Pat. No. 4,177,349 (1979) and McGill, U.S. Pat. No. 4,267,335 (1981). equipped The autoclave was closed purged of air with nitrogen The mixture was heated The addition required 5.5 hours at 190° C.-215° C The autoclave was cooled to 50° C. The oil layer was separated distilled under vacuum