* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With copper(II) choride dihydrate In dimethyl sulfoxide at 100℃; for 7 h;
General procedure: A mixture of starting compound (2.69 mmol), CuCl2.2H2O (10 mol percent) in DMSO (5 mL) stirred at 100 °C. The reaction progress was monitored by thin layer chromatography (PMA was used for stain solution). The reaction mixture was poured into ice cold water. The crude product was purified by column chromatography using ethyl acetate and petroleum ether as eluent to afford carbazoles.
Reference：
[1] Tetrahedron Letters, 2018, vol. 59, # 22, p. 2145 - 2149
[2] Organic and Biomolecular Chemistry, 2014, vol. 12, # 27, p. 4832 - 4836
[3] Journal of the Chemical Society, 1945, p. 530,532
2
[ 108-94-1 ]
[ 589-21-9 ]
[ 21865-50-9 ]
Yield
Reaction Conditions
Operation in experiment
98%
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In ethyl acetate at 110℃; for 0.166667 h; Microwave irradiation; Sealed vessel
General procedure: T3P.(R). (50percent in EtOAc) (0.55-0.68 mmol) was added to a mixture of hydrazine (59 mg, 0.55 mmol) and ketone/aldehyde (0.55 mmol) in a microwave vial. The reaction volume was then made up to 0.5 mL with EtOAc and the vessel was sealed under air. The mixture was heated under microwave irradiation (Biotage Initiator) at 100-150 °C for 5-15 min. The solvent was evaporated under reduced pressure and the oily residue was purified by filtration through a plug of silica gel (eluent: isohexane/EtOAc, 8:2) to yield the desired indole or tetrahydrocarbazole. When the reaction was conducted on a 5 mmol scale the product (3a) was purified by precipitation from acetone/water.
88%
With Amberlite® IR 120 In ethanol at 80℃; for 12 h;
General procedure: A mixture of the carbonyl compound (5, 1.0 mmol), arylhydrazine (6, 1.2 mmol), and the solid acid (7, Amberlite, 1.5 g, obtained from Aldrich Chemical Co.) was refluxed in absolute ethanol (10 ml) for 8 h. The reaction was monitored by thin-layer chromatography(TLC), and upon completion the mixture was cooled to room temperature, the catalyst filtered off, and the product was washed thoroughly with ethylacetate (30 ml). The combined organics were washed with water, dried (Na2SO4), and concentrated in vacuo. The resulting residue was chromatographed on a silicagel column eluting with ethylacetate–hexane mixtures to obtain the purified indole (8). This was fully characterized by infrared, 400-MHz 1H NMR, high-resolution mass spectrometry, and melting point (solids).
Reference：
[1] Tetrahedron Letters, 2011, vol. 52, # 34, p. 4417 - 4420
[2] Synthetic Communications, 2015, vol. 45, # 8, p. 1018 - 1022
[3] Organic and Biomolecular Chemistry, 2014, vol. 12, # 27, p. 4832 - 4836
[4] Chemical Communications, 2003, # 15, p. 1822 - 1823
3
[ 622-88-8 ]
[ 108-94-1 ]
[ 21865-50-9 ]
Yield
Reaction Conditions
Operation in experiment
82%
for 8 h; Reflux
General procedure: A substituted phenyl hydrazine. HCl (4.61 mmol) was added to the mixture of cyclohexanone (4.61 mmol) and acetic acid (15 ml) portion wise for 30 min. The mixture was then refluxed for 8 h and progress of reaction was monitored by thin layer chromatography. The reaction mixture was cooled and poured into crushed ice. The solid product was separated, filtered, dried and recrystallized from the methanol solvent.
74%
for 7 h; Reflux
To a solution of 4-bromophenylhydrazine hydrochloride (2.00 g, 8.95 mmol) inηOAc (13 ml) was added cyclohexanone (0.93 ml, 8.95 mmol). The resulting mixture was heated to reflux for 7 h and then cone, in vacuo. The crude product was dissolved in EtOAc (50 ml), washed with H2O, sat.NaHCO3, dried over MgSO4, filtered and cone, in vacuo. The crude product was purified by silica gel flash chromatography (EtOAc/hexane, 0-30percent) to give the title compound (brown solid, 1.63 g). The yield: 74.0percent.
Stage #1: With hydrogenchloride In water at 60℃; for 4 h; Stage #2: With sodium hydroxide In water
Step 2. 6-Bromo-2,3,4,9-tetrahydro-1H-carbazole; A 250-mL round-bottomed flask was charged with 1-(4-bromophenyl)-2-cyclohexylidenehydrazine (11 g, 41.35 mmol, 1.00 equiv) and conc. HCl (150 mL). The resulting mixture was heated to 60° C. in an oil bath for 4 hours. The reaction progress was monitored by TLC (EtOAc:PE=1:1). Upon completion, the reaction mixture was cooled down to room temperature. The pH was adjusted to 8 with aqueous sodium hydroxide. The resulting mixture was then extracted with ethyl acetate (5.x.100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered off and concentrated on a rotary evaporator. The residue was purified by a silica gel column chromatography eluted with ethyl acetate/petroleum ether (1/10) affording 3-bromo-6,7,8,9-tetrahydro-5H-carbazole as yellow solid (10 g, 97percent).
Reference：
[1] Patent: US8080566, 2011, B1, . Location in patent: Page/Page column 53-54
[2] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1988, vol. 24, p. 154 - 158[3] Khimiya Geterotsiklicheskikh Soedinenii, 1988, vol. 24, # 2, p. 188 - 192
5
[ 108-85-0 ]
[ 673-40-5 ]
[ 21865-50-9 ]
Reference：
[1] Synthesis, 2011, # 1, p. 23 - 29
6
[ 108-94-1 ]
[ 92644-16-1 ]
[ 21865-50-9 ]
Reference：
[1] Chemistry - A European Journal, 2017, vol. 23, # 64, p. 16174 - 16178
7
[ 106-40-1 ]
[ 21865-50-9 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 41, p. 9868 - 9873
8
[ 100116-02-7 ]
[ 106-40-1 ]
[ 21865-50-9 ]
Reference：
[1] Journal of Organic Chemistry, 1959, vol. 24, p. 478,481
With copper(II) choride dihydrate; In dimethyl sulfoxide; at 100℃; for 7h;
General procedure: A mixture of starting compound (2.69 mmol), CuCl2.2H2O (10 mol %) in DMSO (5 mL) stirred at 100 C. The reaction progress was monitored by thin layer chromatography (PMA was used for stain solution). The reaction mixture was poured into ice cold water. The crude product was purified by column chromatography using ethyl acetate and petroleum ether as eluent to afford carbazoles.
Step 2. 6-Bromo-2,3,4,9-tetrahydro-1H-carbazole; A 250-mL round-bottomed flask was charged with 1-(4-bromophenyl)-2-cyclohexylidenehydrazine (11 g, 41.35 mmol, 1.00 equiv) and conc. HCl (150 mL). The resulting mixture was heated to 60 C. in an oil bath for 4 hours. The reaction progress was monitored by TLC (EtOAc:PE=1:1). Upon completion, the reaction mixture was cooled down to room temperature. The pH was adjusted to 8 with aqueous sodium hydroxide. The resulting mixture was then extracted with ethyl acetate (5×100 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered off and concentrated on a rotary evaporator. The residue was purified by a silica gel column chromatography eluted with ethyl acetate/petroleum ether (1/10) affording 3-bromo-6,7,8,9-tetrahydro-5H-carbazole as yellow solid (10 g, 97%).
116.2 g (0.520 mol) of synthesized in [Scheme 1], 51.0 g (0.520 mol) of cyclohexanone, and 1162.0 ml of ethanol were added to a 2 L round bottom flask and refluxed for 10 hours. When the reaction was complete, the reaction solution was concentrated and then column chromatography was used to obtain 128.6 g (yield 98.9%).
98.9%
In ethanol; for 10h;Reflux;
116.2 g (0.520 mol) of <1-d>synthesized in Scheme 1 in a 2 L round bottom flask, Cyclohexanone 51.0 g (0.520 mol) And 1162.0 ml of ethanol were refluxed for 10 hours. After the reaction is over, the reaction solution is concentrated. Column chromatography was carried out to give 128.6g (yield 98.9%).
82%
With acetic acid; for 8h;Reflux;
General procedure: A substituted phenyl hydrazine. HCl (4.61 mmol) was added to the mixture of cyclohexanone (4.61 mmol) and acetic acid (15 ml) portion wise for 30 min. The mixture was then refluxed for 8 h and progress of reaction was monitored by thin layer chromatography. The reaction mixture was cooled and poured into crushed ice. The solid product was separated, filtered, dried and recrystallized from the methanol solvent.
74.0%
In acetic acid; for 7h;Reflux;
To a solution of 4-bromophenylhydrazine hydrochloride (2.00 g, 8.95 mmol) inetaOAc (13 ml) was added cyclohexanone (0.93 ml, 8.95 mmol). The resulting mixture was heated to reflux for 7 h and then cone, in vacuo. The crude product was dissolved in EtOAc (50 ml), washed with H2O, sat.NaHCO3, dried over MgSO4, filtered and cone, in vacuo. The crude product was purified by silica gel flash chromatography (EtOAc/hexane, 0-30%) to give the title compound (brown solid, 1.63 g). The yield: 74.0%.
69%
In ethanol; at 65℃; for 1h;
68.5 g (306.5 mmol) of the compound represented by the formula (1-a) obtained in the above-mentioned scheme 1 and 30.0 g (306.5 mmol) of cyclohexanone were added to 700 ml of ethyl alcohol and stirred at 65 C for 1 hour . When the reaction is completed, the reaction mixture is cooled to room temperature, and the resulting solid is filtered and washed with ethyl alcohol. And dried under reduced pressure at room temperature to obtain 53.0 g of a compound represented by the general formula [1-b]. (Yield 69%)
In acetic acid; for 6h;Heating / reflux;
A sample of 4-bromo phenyl hydrazine hydrochloride (2.235g, 10 mmol) and 4-cyclohexanone (1.03ml, 10 mmol), in 15 ml of AcOH, were refluxed for 6 hrs. The TLC of mixture showed complete consumption of starting material and a new spot with higher Rf value. The mixture was cooled to room temperature, the resulting precipitate was filtered off, dried in vacuo to obtain 1.8g of the pure product.1H NMR 500 MHz CDCl3: 7.70, brs, IH, 7.56, d, J=1.6, IH, 7.18, dd, J=1.8, 8.5, IH, 7.13, d, J=8.5, IH, 2.72, t, J=6, 2H, 2.65, t, J=6.2, 2H, 1.95-1.83, m, 4H.
[02421 Cyclohexanone (1.16 mL, 11.2 mmol) and 4-bromo-phenylhydrazine hydrochloride (2.50 g, 11.2 mmol) were refluxed in cyclohexanone (18 mL) and acetic acid (AcOH) (12 mL) for 24 h. The reaction mixture was treated with saturated sodium bicarbonate (Na2CO3) and extracted with ethyl acetate, dried (Na2CO3) and concentrated. The product was purified by column chromatography, giving 479 mg of compound 30 as a solid.
With sodium hydride; In N,N-dimethyl-formamide; at 80℃;
A sample of 6-Bromo-2,3,4,9-tetrahydro carbazole (0.498g, 2 mmol) was dissolved in 4 ml of dry DMF. To this stirred solution, NaH (60% suspension; 0.24g, 6 mmol) was added portion wise followed by the addition of diethyl sulfate (0.79ml, 6 mmol). The reaction mixture was heated to 80 0C overnight. The TLC of mixture, with 4:6 dichloromethane/hexane, showed complete consumption of starting material and a new spot with higher Rf value. The reaction mixture was added to 60 ml of ice cold H2O, the mixture was extracted with EtOAc and washed with sat. brine solution. The organic layer was dried over anhyd.MgSO4, solvents were concentrated in vacuo and the crude was purified by column chromatography to obtain 0.4g of the pure product.1H NMR 500 MHz CDCl3: 7.57, s, IH, 7.2, d, J=8.7, IH, 7.12, d, J=8.7, IH, 4.04, q, J=7.2, 2H, 2.73-2.64, m, 4H, 1.98-1.90, m, 2H, 1.88-1.81, m, 2H, 1.30, t, J=7.3, 3H.
To a suspension of 39 (0.75 g, 3.0 mmol) in acetic acid (3 ml) is added acetyl chloride (0.21 ml, 3.0 mmol). The mixture is heated to reflux, resulting in a clear solution. After 2 hours, the reaction solution is cooled to room temperature (rt). A solid is precipitated out. The solid 48 is filtered and washed with hexanes (2 x), 0.24 g, 27%
To a solution of 6-bromo-2,3,4,9-tetrahydro-lH-carbazole (150 mg, 0.61 mmol) inDMF (5 ml) was added NaH (60% in mineral oil, 37 mg, 0.92 mmol) and tetrabutylammonium iodide (340 mg, 0.92 mmol). The resulting mixture was stirred at room temperature for 10 min and followed by addition of l-(3-chloropropoxy)-3,5- dimethylbenzene (121 mg, 0.61 mmol). The reaction mixture was stirred at room temperature overnight, poured into H2O (30 ml), and extracted with EtOAc (3 x 30 ml). The organic layers were combined, dried over MgSO4, filtered and cone, in vacuo. The crude product was purified by silica gel flash chromatography (EtOAc/hexane, 0-20%) to give the title compound (colorless oil, 182 mg). The yield: 72.4%.
To a solution of 6-bromo-2,3,4,9-tetrahydro-lH-carbazole (66 mg, 0.27 mmol) inDMF (3 ml) was added NaH (60% in mineral oil, 16 mg, 0.41 mmol) and tetrabutylammonium iodide (151 mg, 0.41 mmol). The resulting mixture was stirred at room temperature for 10 min and followed by addition of l-(3-chloropropoxy)-3,5- difluorobenzene (55 mg, 0.27 mmol). The reaction mixture was stirred at room temperature overnight, poured into H2O (30 ml), and extracted with EtOAc (3 x 30 ml). The organic layers were combined, dried over MgSO4, filtered and cone, in vacuo. The crude product was purified by silica gel flash chromatography (EtOAc/hexane, 0-20%) to give the title compound (colorless oil, 53 mg). The yield: 46.7%.
Step 3. 6-Bromo-9-ethyl-2,3,4,9-tetrahydro-1H-carbazole; A 500-mL round-bottomed flask was charged with 3-bromo-6,7,8,9-tetrahydro-5H-carbazole (5 g, 20.08 mmol, 1.00 equiv) in N,N-dimethylformamide (270 mL). To this solution was added sodium hydride (1.2 g, 30.00 mmol, 1.50 equiv, 60%) in several batches at -10 C., followed by addition of iodoethane (6.26 g, 40.13 mmol, 2.00 equiv) as a solution in N,N-dimethylformamide (30 mL) drop wise -10 C. The resulting mixture was stirred at room temperature for 30 minutes. The reaction progress was monitored by TLC (EtOAc:PE=1:1). Upon completion, the reaction was then quenched by the addition of water/ice (120 mL). Then, the mixture was extracted with ethyl acetate (4×80 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered off and concentrated on a rotary evaporator. The residue was purified by a silica gel column chromatography eluted with ethyl acetate/petroleum ether (1/20) affording 3-bromo-9-ethyl-6,7,8,9-tetrahydro-5H-carbazole as brown oil (5 g, 90%).
With tert.-butylhydroperoxide; methanesulfonic acid; iron(II) phthalocyanine; acetic acid; In acetonitrile; for 0.0833333h;Cooling with ice;
Dissolve 125 mg of S6 in acetonitrile.Add 154 mg of 3,4-dihydroxybenzoic acid,Add 7 mg under ice bath Iron phthalocyanine, 30 mg of acetic acid,4.8 mg of methanesulfonic acid and 135 mg of tert-butyl hydroperoxide, After stirring the reaction for 5 minutes under the same conditions,After monitoring the reaction,Dilute with 20 mL of ethyl acetate and extract 20 mL of H2O.The combined organic layers were then washed with 20 mL of saturated brine.Dry with anhydrous Na2SO4, filter and spin dry.By silica gel chromatography (PE/EtOAc) = 2:1) Purify the crude product,127 mg of compound 6,The reaction yield is 64%.The product was a white solid at room temperature.Physical state: white solid; melting point: 149.1-150.2 C
2-chloro-4-(dibenzo[b,d]thiophen-4-yl)-6-phenyl-1,3,5-triazine[ No CAS ]
C33H23BrN4S[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
43%
23.6 g (63.17 mmol) of the compound represented by the formula [1-b] obtained from the above-mentioned scheme 2 and 3.3 g (82.1 mmol) of 60% sodium hydride were placed in 200 ml of dimethylformamide and stirred at room temperature for 30 minutes . Thereafter, 15.7 g (63.17 mmol) of the compound represented by the formula [3-b] obtained from the above-mentioned Reaction Scheme 13 was dissolved in 150 ml of dimethylformamide, and the mixture was slowly added dropwise, followed by stirring for 1 hour. After completion of the reaction, 20 ml of distilled water was added, followed by filtration and recrystallization to obtain 16.0 g of a compound represented by the formula (3-c). (Yield: 43%)
With 18-crown-6 ether; copper; potassium carbonate; In 1,2-dichloro-benzene; at 180℃; for 24h;
9.9 g (31.4 mmol) of the compound of the formula (1-b) obtained from the above scheme 2 and 4.0 g (62.8 mmol) of the copper powder obtained in the above Reaction Scheme 35, , 1.7 g (6.3 mmol) of 18-crown-6 and 8.7 g (62.8 mmol) of potassium carbonate were added in this order. 90 ml of 1,2-dichlorobenzene was added thereto and the mixture was refluxed and stirred at 180 C for 1 day. After the completion of the reaction, the solution was concentrated under reduced pressure, and the organic layer solution was recrystallized from methylene chloride and acetone to obtain 9.2 g of a compound represented by the following formula 8-b. (Yield: 53%)
With potassium phosphate; copper(l) iodide; (1R,2R)-1,2-diaminocyclohexane; In 1,4-dioxane; for 12h;Reflux;
In a 1 L round-bottom flask, 60.0 g (0.240 mol) of synthesized in [Scheme 2], 73.4 g (0.360 mol) of iobenzene, 2.3 g (0.012 mol) of copper iodide (CuI),Tripotassium phosphate (K3PO4) 106.96 g (0.504 mol),54.8 g (0.480 mol) of trans-1,2-cyclohexanediamineAnd 300.0 ml of 1,4-dioxane was added and refluxed for 12 hours. After the reaction was completed, the mixture was cooled to room temperature, extracted with 1 L of water, and the organic layer was anhydrous and concentrated under reduced pressure. Then, 72.0 g (yield 92.0%) of was obtained by using an adsorption column chromatography.
92%
With potassium phosphate; copper(l) iodide; trans-1,2-cyclohexanediamine; In 1,4-dioxane; for 12h;Reflux;
60.0 g (0.240 mol) of <1-e> synthesized in Scheme 5 in a 1 L round bottom flask, Iobenzene 73.4g (0.360mol), Cooper iodide (CuI) 2.3 g (0.012 mol), Tripotassium phosphate (K3PO4) 106.96g (0.504mol), 54.8 g (0.480 mol) of trans-1,2-cyclohexanediamine And 300.0ml of 1,4-dioxane was added and refluxed for 12 hours. After the reaction was completed, the mixture was cooled to room temperature, extracted with 1L of water, and the organic layer was treated with anhydrous and concentrated under reduced pressure, followed by adsorption column chromatography. 72.0 g (yield 92.0%) of were obtained <1-f>.
87%
With copper; potassium carbonate; In 1,2-dichloro-benzene; at 180℃; for 24h;
41.0 g (163.9 mmol) of the compound represented by the formula 1-b, 66.9 g (327.8 mmol) of the iodobenzene, 20.8 g (327.8 mmol) of the copper powder and 8.7 g (32.8 mmol) of potassium carbonate and 68.0 g (491.7 mmol) of potassium carbonate were added in this order, 410 ml of 1,2-dichlorobenzene was added thereto, and the mixture was refluxed and stirred at 180 C for 1 day. After completion of the reaction, the solution was concentrated under a high-temperature filter, and then subjected to column chromatography using hexane alone to obtain 46.5 g of a compound represented by the formula (1-c). (Yield: 87%)
66.3%
With potassium phosphate; copper(l) iodide; rac-diaminocyclohexane; In 1,4-dioxane; for 12h;Reflux;
While purging with nitrogen gas in a 1L round bottom flask at room temperature,<strong>[21865-50-9]6-bromo-1,2,3,4-tetrahydrocarbazole</strong> (100 g, 400 mmol),Iodinebenzene (122 g, 600 mmol),Copper iodide (3.80 g, 20.0 mmol),Potassium phosphate (178g, 840mmol),1,2-cyclohexane diamine (91.3 g, 800 mmol),1,4-dioxane (500 mL) was added and refluxed for 12 hours. After TLC confirms the end of the reaction,After cooling the reaction solution to room temperature,Methylene chloride and water were added to separate the layers. The aqueous layer was removed and the organic layer was concentrated under reduced pressure,Purification by silica gel column chromatography gave <1-a>(86.5 g, 265 mmol). (Yield 66.3%)
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
