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Stage #1: at 0 - 20℃; for 16 h; Stage #2: With water; ammonium chloride In ethyl acetate
[00354] Cyclopropylmagnesium bromide (15OmL, 0.5M in tetrahydrofuran) was slowly added to a solution of 1 -bromonaphthalene (1Og, 50mmol) and [l ,3-bis(diphenylphosphino)ρroρane] dichloro nickel (II) in tetrahydrofuran (1OmL) stirred at 0°C, and the reaction mixture stirred at room temperature for 16 hours. The solvent was removed under reduced pressure and ethyl acetate and aqueous ammonium chloride were added- After extraction, the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield l-cyclopropylnaphthalcne (6.4g, 76percent).
76%
at 0 - 20℃; for 16 h;
Cyclopropylmagnesium bromide (150 niL, 0.5 M in tetrahydrofuran) was slowly added to a solution of 1-bromo-naphthalene (10 g, 50 mmol) and [1,3- bis(diphenylphosphino)propane]dichloronickel(II) in tetrahydrofuran (10 niL) stirred at 0 0C. The reaction mixture was stirred at room temperature for 16 hours and the solvent was evaporated under reduced pressure. EtOAc and ammonium chloride in water were added. After extraction, the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield 1 -cyclopropyl-naphthalene (6.4 g, 76percent).
76%
at 0 - 20℃;
STEP A: 1-CyclopropylnaphthaleneCyclopropylmagnesium bromide (150 mL, 0.5M in tetrahydrofuran) was slowly added to a solution of 1-bromonaphthalene (10 g, 50 mmol) and [l,3-bis(diphenylphosphino)propane] dichloro nickel (II) in tetrahydrofuran (10 mL) stirred at 0 °C, and the reaction mixture stirred at room temperature for 16 hours. The solvent was removed under reduced pressure and ethyl acetate and aqueous ammonium chloride were added. After extraction, the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield 1-cyclopropylnaphthalene (6.4 g, 76percent).
With potassium phosphate monohydrate; palladium diacetate; XPhos In <i>tert</i>-butyl alcohol at 50℃; for 12 h; Schlenk technique; Inert atmosphere; Sealed tube
General procedure: Procedure A: To a Schlenk tube equipped with a magnetic stiring bar and a teflon septum was charged K3PO4.H2O (1.5 mmol, 3 equiv), aryl pentafluorobenzene sulfonate (0.5 mmol, 1.0 equiv), aryl boronic acid (0.75 mmol, 1.5 equiv) and Pd(PPh3)2Cl2 (0.015 mmol, 3 molpercent). The tube was then capped with a rubber septum, evacuated and backfilled with nitrogen and this cycle was repeated twice. Under an inertatmosphere, tert - butanol (3 mL) was added via syringe. Under a positive pressure of nitrogen, the rubber septum was replaced with a Teflon screw cap and this was sealed. The Schlenk tube was stirred at room temperature for the time indicated. When the reaction was completed according to TLC or GCMS (FID), thereaction mixture was diluted with EtOAc (5 mL) and filtered through celite bed. The organic layer was concentrated under reduced pressure. The residue was purified through silica gel (230 - 400 mesh) column chromatography using 1-10percent ethyl acetate in petroleum ether to afford the product. Procedure B: Similar procedure as A except that Pd(OAc)2 (3 molpercent) and Xphos (5 molpercent) instead of Pd(PPh3)2Cl2 as catalyst system.
With potassium phosphate tribasic heptahydrate; C45H53ClFeNO2PPd In water; toluene at 100℃; for 5 h; Inert atmosphere
General procedure: Potassium phosphate (0.75 mmol) and IIe (1 mol percent) was added to the solution of aryl halides (0.25 mmol) and cyclopropylboronic acid (0.5 mmol) in toluene (2.0 mL) and water (100 μL). The mixture was heated to 100 °C for a proper time under nitrogen atmosphere and cooled to room temperature. Water (10 mL) was added and the mixture was extracted with EtOAc (3.x.15 mL), evaporated and purified by chromatography on silica gel.
With sodium hydroxide; hydrazine; 2,2'-[1,2-ethanediylbis(oxy)]bisethanol In water for 5 h; Heating
General procedure: 3-dimethylamino-1-(naphthalen-1-yl)propan-1-one hydrochloride (50g, El equivalents) andtriethylene glycol (100 ml) were charged to the reactor at room temperature. 50percent NaOH (E2equivalents) was added while keeping the internal temperature at room temperature. 64percent hydrazine solution in water (E3 equivalents) was added dropwise followed by heating the reaction mixture to a temperature of 80±5°C for a period of 5 hours. Thereafter, water was distilled off in a vacuum of 30-40mbar at a temperature of 80±5°C. The precipitated salt was separated from the reaction mixture by filtration at a temperature of approximately 80°C andsubsequently washed with triethylene glycol brought to a temperature of approximately 80°C (20 Volpercent of the total amount of triethylene glycol).Bringing the reaction mixture to a temperature of 200±10°C for a period of about 5 hours gave crude 1-cyclopropyl-napthalene which was isolated by azeotropic distillation at a temperature of 190±10°C in a vacuum of 30-40mbar. For further purification and isolation ofthe obtained product water was added to the distillate and the product extracted with methyl tert.-butyl ether. The organic phase was washed with water and distilled in a vacuum of 50- lOOmbar at a temperature of 80°C.The isolated pure 1-cyclopropyl-naphtalene was obtained as clear, colorless or pale yellow liquid with a boiling point of 152°C at 13 Torr.
With dibromohydantoin,; In dichloromethane; at 30 - 50℃;
300 mL of dichloromethane, <strong>[25033-19-6]1-cyclopropylnaphthalene</strong> (30 g, 178 mmol), dibromohydantoin (50.9 g, 178 mmol) were placed in a dry reaction flask.Control the internal temperature of 30 ~ 50 C, stir the reaction until TLC detection reaction is complete,Stop the insulation.Wash with 100 mL of sodium hydrogen sulfite solution (5%).Wash with 100 mL of sodium hydroxide solution (5%) and wash to neutrality.Evaporation to dryness under reduced pressure gave 4-cyclopropyl-1-bromonaphthalene (39.8 g, yield: 90.48%, purity 97.6%).
90%
With N-Bromosuccinimide; In acetonitrile; at 50℃; for 24h;
1-Cyclopropylnaphthalene (5.0 g, 30 mmol) was dissolved in 50 mL of acetonitrile, NBS (7.1 g, 40 mmol) was added, and the mixture was reacted at 50 C for 24 hours. After completion of the reaction, the reaction solution was cooled to room temperature, concentrated to remove acetonitrile, and 50 mL of n-hexane. The filtrate was concentrated and purified through a silica gel column to yield 6.7 g of 4-cyclopropyl-1-bromonaphthalene, yield 90%.
88%
With N-Bromosuccinimide; In acetonitrile; at 30 - 40℃; for 24h;
General procedure: To a stirred solution of 1-(cyclo)alkylnaphthalene (2a-2e, 0.13 mol) in MeCN (200 mL) at room temperature was added NBS (24.92 g, 0.14 mol), and the resulting mixture was stirred at 30-40C until completion of the reaction as indicated by TLC analysis (typically within 24 h). On cooling to room temperature, the reaction mixture was poured into ice-water (800 mL), and the resulting mixture was extracted with CH2Cl2 (300 mL 3). The combined extracts were washed successively with saturated aqueous Na2CO3 (200 mL 5) and 5% brine (500 mL), dried (Na2SO4) and evaporated on a rotary evaporator to give a residue, which was purified by column chromatography to afford the pure product 3a-3e. 1-bromo-4-cyclopropylnaphthalene (3a). Colorless oil, 28.27 g (88%). 1H NMR (DMSO-d6, 400 MHz) : 8.43-8.47(m, 1H), 8.13-8.17 (m, 1H), 7.75 (d, 1H, J = 7.6 Hz), 7.66-7.72 (m, 2H), 7.15-7.17 (m, 1H), 2.34-2.41 (m, 1H), 1.03-1.08 (m, 2H), 0.69-0.73 (m, 2H).
81%
With N-Bromosuccinimide; In acetonitrile; at 20℃;
Commercially available compound II-A (8.41 g, 50 mmol) was dissolved in acetonitrile (150 mL) and stirred at room temperature, to which was added NBS (10.68 g, 60 mmol). The resulting reaction mixture was stirred at room temperature overnight, at which point TLC indicated the completion of the reaction. (0030) The reaction mixture was poured into ice water (500 mL), stirred, and extracted with CH2Cl2 (200 mL x 3). The organic phases were combined, washed successively with saturated Na2CO3 solution (100 mL x 3) and 5% saline solution (200 mL), and dried over anhydrous Na2SO4. The dried organic phase was evaporated on a rotary evaporator to remove the solvent, and the resulting residue was purified by column chromatography to give the product II-1 as a colorless oily substance, yield: 10.01 g, 81%. 1H NMR (DMSO-d6, 400 MHz), delta 8.43-8.47 (m, 1H), 8.13-8.17 (m, 1H), 7.75 (d, 1H, J = 7.6 Hz), 7.66-7.72 (m, 2H), 7.15-7.17 (m, 1H), 2.34-2.41 (m, 1H), 1.03-1.08 (m, 2H), 0.69-0.73 (m, 2H).
With potassium phosphate tribasic heptahydrate; C45H53ClFeNO2PPd; In water; toluene; at 100℃; for 5h;Inert atmosphere;
General procedure: Potassium phosphate (0.75 mmol) and IIe (1 mol %) was added to the solution of aryl halides (0.25 mmol) and cyclopropylboronic acid (0.5 mmol) in toluene (2.0 mL) and water (100 muL). The mixture was heated to 100 C for a proper time under nitrogen atmosphere and cooled to room temperature. Water (10 mL) was added and the mixture was extracted with EtOAc (3×15 mL), evaporated and purified by chromatography on silica gel.
To a dry 5L round bottom flask, 1-bromonaphthalene (414.0 g, 2 mol) was added.[1,3-bis(diphenylphosphino)propane]nickel chloride (165 g, 0.4 mol) and 1500 mL of dry THF, stirred in an ice water bath and cooled.A 1000 mL/L solution of cyclopropylmagnesium bromide in THF was added dropwise to the system using a constant pressure dropping funnel. After the addition was completed, the reaction mixture was stirred at room temperature for 8 h under nitrogen.Then the temperature was raised to reflux and the reaction was carried out for 36 h.After the reaction was completed, the reaction mixture was cooled to room temperature.Then carefully pour into 10L of stirred ice water and stir.The pH was adjusted to 2 with concentrated hydrochloric acid, and extracted with CH2Cl2 (4000 mL×3).The organic phases were combined, washed with 3000 mL of 5% sodium chloride solution and dried over anhydrous Na2SO4.The solvent was evaporated on a rotary evaporator, and the obtained residue was added to 5 L of n-hexane and 10 L of toluene, and the mixture was stirred for 1 hour, and the mixture was allowed to stand, and the organic layer was discarded to obtain a colorless liquid 313 g (yield: 87.2%).
82.23%
With iron(III) chloride; In tetrahydrofuran; at 20℃; for 29h;Inert atmosphere; Cooling with ice; Reflux;
Under the protection of nitrogen,In a dry 2L round bottom flask,Add 1-bromonaphthalene (50g, 241mmol),Ferric chloride (2.0g, 12.3mmol)And 100 mL of dry tetrahydrofuran (THF),Stir under ice cooling,Slowly move to the system with a constant pressure dropping funnel300 mL of a 1.0 mol/L cyclopropylmagnesium bromide in THF was added dropwise.After the addition was completed, the reaction mixture was stirred at room temperature under nitrogen for 5 h.The temperature was then raised to reflux and allowed to react for 24 h.After the reaction is completed, most of the solvent is removed by distillation under reduced pressure.Cool the residue to room temperature,Slowly pour into 2L of stirred ice water and stir.The pH was adjusted to 2 to 3 with concentrated hydrochloric acid and extracted with dichloromethane (250 mL × 3).The organic phases were combined and washed with 500 mL of water.Evaporate under reduced pressure1-cyclopropylnaphthalene (33.4 g, yield 82.23%, purity 96.4%)
76%
[00354] Cyclopropylmagnesium bromide (15OmL, 0.5M in tetrahydrofuran) was slowly added to a solution of 1 -bromonaphthalene (1Og, 50mmol) and [l ,3-bis(diphenylphosphino)rhororhoane] dichloro nickel (II) in tetrahydrofuran (1OmL) stirred at 0C, and the reaction mixture stirred at room temperature for 16 hours. The solvent was removed under reduced pressure and ethyl acetate and aqueous ammonium chloride were added- After extraction, the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield l-cyclopropylnaphthalcne (6.4g, 76%).
76%
{1,3-bis(diphenylphosphino)-propane}dichloronickel (II); In tetrahydrofuran; at 0 - 20℃; for 16h;
Cyclopropylmagnesium bromide (150 niL, 0.5 M in tetrahydrofuran) was slowly added to a solution of 1-bromo-naphthalene (10 g, 50 mmol) and [1,3- bis(diphenylphosphino)propane]dichloronickel(II) in tetrahydrofuran (10 niL) stirred at 0 0C. The reaction mixture was stirred at room temperature for 16 hours and the solvent was evaporated under reduced pressure. EtOAc and ammonium chloride in water were added. After extraction, the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield 1 -cyclopropyl-naphthalene (6.4 g, 76%).
76%
1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In tetrahydrofuran; at 0 - 20℃;
STEP A: 1-CyclopropylnaphthaleneCyclopropylmagnesium bromide (150 mL, 0.5M in tetrahydrofuran) was slowly added to a solution of 1-bromonaphthalene (10 g, 50 mmol) and [l,3-bis(diphenylphosphino)propane] dichloro nickel (II) in tetrahydrofuran (10 mL) stirred at 0 C, and the reaction mixture stirred at room temperature for 16 hours. The solvent was removed under reduced pressure and ethyl acetate and aqueous ammonium chloride were added. After extraction, the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield 1-cyclopropylnaphthalene (6.4 g, 76%).
With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In tetrahydrofuran; at 0 - 5℃;
[0345] Under this route, cyclopropylmagnesium bromide was added to a solution of bromonaphthalene in tetrahydrofuran stirred at 0-5 C in the presence of a catalytic amount of [l,3-bis(diphenylphosphino)propane]dichloronickel(II) to form cyclopropylnaphthalene, which was diluted with ethyl acetate and washed. [0346] Cyclopropylnaphthalene (Compound 6) was dissolved in dichloromethane or 1 ,2- dichlorobenzene, then nitric acid was added at 0 C and the reaction mixture was allowed to warm to ambient temperature. After reaction completion, the mixture was neutralized with sodium bicarbonate then washed with water, and l-cyclopropyl-4-nitronaphthalene (Compound 7) was used in the next step without further purification. [0347] Compound 7 was dissolved in ethanol or methanol, and hydrogenated in the presence of palladium on charcoal. The resulting l-amino-4-cyclopropylnaphthalene (Compound 8) was crystallized as an oxalate salt (Compound 8 -A) then dissolved in dichloromethane or toluene and treated with thiophosgene in the presence of potassium hydroxide to generate the corresponding isothiocyanate intermediate (Compound 9). [0348] l-Cyclopropyl-4-isothiocyanatonaphthalene (Compound 9) was solvent exchanged with DMF and condensed with aminoguanidine hydrochloride to generate the corresponding substituted thiosemicarbazide (Compound 13). This intermediate Compound 13 was heated in the presence of aqueous sodium hydroxide to form Compound 11 , which was purified by crystallization from a mixture of ethanol and water or a mixture of methanol, DMF and water.
With nitric acid; acetic acid; at 20℃; for 7h;Cooling with ice;
To a 10 L reactor, <strong>[25033-19-6]1-cyclopropylnaphthalene</strong> (253 g, 1.5 mol) and 3000 mL of glacial acetic acid were added, and the mixture was stirred under ice-cooling, and 500 mL of concentrated nitric acid was slowly added dropwise. After the addition was completed, the reaction mixture was stirred at room temperature for further 7 h.After the reaction was completed, the reaction mixture was poured into 6 L of stirred ice water.Stirring was continued for 20 min and extracted with CH 2 Cl 2 (1000 mL×3). Combine the organic phase,Wash with saturated NaHCO3 solution until the pH of the aqueous phase is greater than 7,Wash with 1500 mL of 5% sodium chloride solution and dry with anhydrous Na2SO4.The solvent was evaporated on a rotary evaporator, and the obtained residue was added to 3 L of n-hexane and 4 L of toluene. The mixture was stirred for 1 hour, and the mixture was allowed to stand for separation. The organic layer was discarded to give 284 g of pale yellow liquid, yield 85.9%.
64%
With sodium nitrite; at 0℃; for 2.5h;
[00355] Sodium nitrite (3OmL) was slowly added (over 2 hours) to 1 -cyclopropylnaphthalene (6.4g,38mmol) stirred at OC. The reaction mixture was stirred at OC for an extra 30 min and then slowly poured into ice. Water was added, followed by ethyl acetate. After extraction, the organic layer was <n="91"/>washed with aqueous sodium hydroxide (1%) and water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield l-cyclopropyl-4-nitronapbthalene (5.2g. 64%).
64%
With sodium nitrite; at 0℃; for 2.5h;
Sodium nitrite (30 mL) was slowly added (over 2 hours) to 1 -cyclopropyl- naphthalene (6.4 g, 38 mmol) stirred at 0 0C. The reaction mixture was stirred at 0 0C for an extra 30 min and then was slowly poured into ice. Water was added, followed by EtOAc. After extraction, the organic layer was washed with a 1% aqueous solution of NaOH, then washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield 1- cyclopropyl-4-nitro-naphthalene (5.2 g, 64%).
64%
With sodium nitrite; at 0℃; for 2.5h;
STEP B: l-Cyclopropyl-4-nitronaphthaleneSodium nitrite (30 mL) was slowly added (over 2 hours) to <strong>[25033-19-6]1-cyclopropylnaphthalene</strong> (6.4 g, 38 mmol) stirred at 0 C. The reaction mixture was stirred at 0 C for an extra 30 min and then slowly poured into ice. Water was added, followed by ethyl acetate. After extraction, the organic layer was washed with aqueous sodium hydroxide (1%) and water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography to yield l-cyclopropyl-4-nitronaphthalene (5.2 g, 64%).
With nitric acid; at 0 - 20℃;
[0345] Under this route, cyclopropylmagnesium bromide was added to a solution of bromonaphthalene in tetrahydrofuran stirred at 0-5 C in the presence of a catalytic amount of [l,3-bis(diphenylphosphino)propane]dichloronickel(II) to form cyclopropylnaphthalene, which was diluted with ethyl acetate and washed. [0346] Cyclopropylnaphthalene (Compound 6) was dissolved in dichloromethane or 1 ,2- dichlorobenzene, then nitric acid was added at 0 C and the reaction mixture was allowed to warm to ambient temperature. After reaction completion, the mixture was neutralized with sodium bicarbonate then washed with water, and l-cyclopropyl-4-nitronaphthalene (Compound 7) was used in the next step without further purification. [0347] Compound 7 was dissolved in ethanol or methanol, and hydrogenated in the presence of palladium on charcoal. The resulting l-amino-4-cyclopropylnaphthalene (Compound 8) was crystallized as an oxalate salt (Compound 8 -A) then dissolved in dichloromethane or toluene and treated with thiophosgene in the presence of potassium hydroxide to generate the corresponding isothiocyanate intermediate (Compound 9). [0348] l-Cyclopropyl-4-isothiocyanatonaphthalene (Compound 9) was solvent exchanged with DMF and condensed with aminoguanidine hydrochloride to generate the corresponding substituted thiosemicarbazide (Compound 13). This intermediate Compound 13 was heated in the presence of aqueous sodium hydroxide to form Compound 11 , which was purified by crystallization from a mixture of ethanol and water or a mixture of methanol, DMF and water.
With nitric acid;
The compound (L-1) 1-nitro-4-cyclopropylnaphthalene was prepared by reacting <strong>[25033-19-6]1-cyclopropylnaphthalene</strong> as a starting material with nitric acid. The compound (L-1), iron perchlorate hexahydrate was added to ethanol, heated to reflux, hydrazine hydrate was added dropwise and reacted to obtain compound (L-2).
naphthalen-1-yl 2,3,4,5,6-pentafluorobenzenesulfonate[ No CAS ]
[ 411235-57-9 ]
[ 25033-19-6 ]
Yield
Reaction Conditions
Operation in experiment
89%
With potassium phosphate monohydrate; palladium diacetate; XPhos; In tert-butyl alcohol; at 50℃; for 12h;Schlenk technique; Inert atmosphere; Sealed tube;
General procedure: Procedure A: To a Schlenk tube equipped with a magnetic stiring bar and a teflon septum was charged K3PO4.H2O (1.5 mmol, 3 equiv), aryl pentafluorobenzene sulfonate (0.5 mmol, 1.0 equiv), aryl boronic acid (0.75 mmol, 1.5 equiv) and Pd(PPh3)2Cl2 (0.015 mmol, 3 mol%). The tube was then capped with a rubber septum, evacuated and backfilled with nitrogen and this cycle was repeated twice. Under an inertatmosphere, tert - butanol (3 mL) was added via syringe. Under a positive pressure of nitrogen, the rubber septum was replaced with a Teflon screw cap and this was sealed. The Schlenk tube was stirred at room temperature for the time indicated. When the reaction was completed according to TLC or GCMS (FID), thereaction mixture was diluted with EtOAc (5 mL) and filtered through celite bed. The organic layer was concentrated under reduced pressure. The residue was purified through silica gel (230 - 400 mesh) column chromatography using 1-10% ethyl acetate in petroleum ether to afford the product. Procedure B: Similar procedure as A except that Pd(OAc)2 (3 mol%) and Xphos (5 mol%) instead of Pd(PPh3)2Cl2 as catalyst system.
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