* 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.
Reference：
[1] Bulletin de la Societe Chimique de France, 1996, vol. 133, # 1, p. 75 - 82
[2] Journal of Organometallic Chemistry, 1990, vol. 384, p. 193 - 197
With potassium fluoride; iodine In 1,4-dioxane at 80℃; for 1 h;
General procedure: A mixture of the arylboronic acid (0.55mmol), KF (96mg, 1.65mmol) and I2 (127mg, 0.50mmol) in 1,4-dioxane (5mL) was stirred at 80°C for 1h. Then it was filtered through silica gel, eluting with Et2O (10mL) and the solvent was removed by rotary evaporation. When necessary, the product was purified by chromatography on silica gel (petroleum ether/Et2O 98:2).
73%
With iodine; potassium carbonate In acetonitrile at 80℃; for 9 h; Inert atmosphere; Schlenk technique; Sealed tube
General procedure: Arylboronic acid 1 (0.5 mmol) and K2CO3 (1 mmol, 138.0mg) were added to a 20 mL Schlenk-tube equipped with amagnetic stir bar. The tube was evacuated twice and backfilledwith N2. MeCN (2 mL) and I2 (0.75 mmol, 191 mg)were added to the tube at r.t. under a stream of N2, and thetube was sealed and placed into a pre-heated oil bath at 80 °Cfor 8–12 h. The resulting solution was cooled to r.t. and H2O(10 mL) was added. The aq layer was extracted with EtOAc (3 × 5 mL). For products 2s and 2t, HCl (1 M) was added tothe aq solution until pH 2 before extraction. The combinedorganic phase was dried over anhydrous Na2SO4, filteredand concentrated by rotary evaporation. Purification of theresidue by column chromatography on silica gel providedthe desired product 2a–v
Reference：
[1] Chemistry - A European Journal, 2011, vol. 17, # 20, p. 5652 - 5660
[2] Tetrahedron Letters, 2015, vol. 56, # 9, p. 1122 - 1123
[3] Synlett, 1998, # 2, p. 141 - 142
[4] Synlett, 2014, vol. 25, # 7, p. 995 - 1000
6
[ 456-39-3 ]
[ 625-99-0 ]
Yield
Reaction Conditions
Operation in experiment
95%
With potassium iodide In water at 25℃; for 0.0833333 h;
General procedure: To a suspension of aryl diazofluoroborate (1 mmol) inwater (3mL), aqueous solution of potassium iodide (1.5 mmol in 2mL H2O) was added in single lot at room temperature.Reaction mixture was stirred for specific time (Table 2).The solid product was separated by filtration and the liquidproducts were separated by extraction in diethyl ether (5mL).The organic layer was dried over anhydrous Na2SO4 andsolvent was removed at room temperature afforded pure iodocompounds in excellent yields. Further all synthesized compoundswere characterized and confirmed by comparisonwith reported aryl iodides.
Reference：
[1] Letters in Organic Chemistry, 2018, vol. 15, # 7, p. 594 - 599
[2] Synthetic Communications, 1981, vol. 11, # 8, p. 639 - 642
7
[ 535-80-8 ]
[ 625-99-0 ]
Yield
Reaction Conditions
Operation in experiment
84%
With N-iodo-succinimide; [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(lll) hexafluorophosphate; iodine; caesium carbonate In 1,2-dichloro-ethane at 50℃; for 24 h; Inert atmosphere; Irradiation; Sealed tube
General procedure: To a 15 mL test tube with septum Cs2CO3 (0.6 mmol, 195 mg), aromaticcarboxylic acid (1) (0.3 mmol), [Ir(dF(CF3)ppy)2dtbbpy]PF6 (D) (6 μmmol, 6.7 mg), NIS (1.5mmol, 337.5 mg) and I2 (60 μmol, 20 molpercent) were added. The tube was evacuated and backfilledwith argon for three times, and then 3 mL of dry DCE was added through a syringer under argon.The tube was sealed with Parafilm Mr® and placed in an oil bath with a contact thermometer, andthe reaction was carried out at 50 °C under irradiation with 6 × 5 W blue LEDs (λmax = 455 nm).After 24 h or 36 h, the resulting mixture was filtered through a 2 cm thick pad of silica, and thesilica was washed with DCM) (50 mL). The filtrate was collected and the solvent was removed invacuo. The crude residue was purified by silica gel flash column chromatography to provide thetarget product (2). (Note: The reaction was very sensitive to moisture, and the yields sharplydecreased to less than 5percent when 0.01 equivalent of H2O was added to the reaction system).
Reference：
[1] Chemistry - A European Journal, 2017, vol. 23, # 70, p. 17697 - 17700
26
[ 383-63-1 ]
[ 625-99-0 ]
[ 321-31-3 ]
Yield
Reaction Conditions
Operation in experiment
88%
Stage #1: With isopropylmagnesium chloride In tert-butyl methyl ether at -20 - -10℃; for 1 h; Stage #2: at -20 - 20℃;
Accurate weighing of m-chloroiodobenzene (3-chloroiodobenzene) (23.85 g, 0.1 mol) was dissolved in 120 ml of methyl tert-butyl ether and the ethanol cooled ice bath cooled to a negative temperature of 20 to minus 10 ° C. A solution of isopropylmagnesium chloride (0.13 mol) was added dropwise and incubated for 1 hour at a negative 20 to minus 10 ° C after completion of the dropwise addition. Then, trifluoroacetate (18.4 g, 0.13 mol) was added dropwise at this temperature. After completion of the dropwise addition, the mixture was stirred and cooled to room temperature, and then hydrochloric acid (30 ml, 0.3 mol) was added dropwise. The organic layer was removed under reduced pressure to give 20.5 g of crude 2,2,2-trifluoro-(3'-chlorophenyl)ethanone and distilled to give 18.3 g of a colorless transparent liquid, content of 95.9.7percent, the yield of 88percent.
Reference：
[1] Patent: CN106518636, 2017, A, . Location in patent: Paragraph 0117; 0118; 0119; 0120
27
[ 625-99-0 ]
[ 76-05-1 ]
[ 321-31-3 ]
Reference：
[1] Canadian Journal of Chemistry, 1980, vol. 58, p. 2497 - 2503
28
[ 625-99-0 ]
[ 74-86-2 ]
[ 766-83-6 ]
[ 5216-30-8 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 5, p. 449 - 451
With copper; potassium carbonate; In nitrobenzene; at 210℃; for 12h;Inert atmosphere;
Under a stream of nitrogen 1H-indole (100g, 854.0 mmol), 1-chloro-3-iodobenzene (244.3 g, 1024.8 mmol), Cu (27.2g, 427.0 mmol), K2CO3 (236.1 g, 1.70 mol) and nitrobenzene (3000 ml ), and the mixture was stirred for 12 hours at 210 . After the reaction was terminated by the removal of water and then extracted with ethyl acetate and MgSO4, purified by column chromatography (Hexane: EA = 7: 1 (v / v)) to give 1- (3-chlorophenyl) -1H-indole (171.0 to g, a yield of 88%)
88%
With copper; potassium carbonate; In nitrobenzene; at 210℃; for 12h;Inert atmosphere;
Under a stream of nitrogen 1H-indole (100g, 854.0 mmol), 1-chloro-3-iodobenzene (244.3 g, 1024.8 mmol), Cu (27.2g, 427.0 mmol), K2CO3 (236.1 g, 1.70 mol) and nitrobenzene (3000 ml ), and the mixture was stirred for 12 hours at 210 . After the reaction was completed, the organic layer extracted with ethyl acetate, and, to eliminate moisture over MgSO4 column chromatography (Hexane: EA = 8: 1 (v / v)) to give 1- (3-chlorophenyl) -1H in -indole (171.0 g, yield 88%) was obtained.
87%
With potassium phosphate; copper; In dimethyl sulfoxide; at 80℃; for 5h;Inert atmosphere;
General procedure: An oven dried two-necked round bottom flask was charged with aryl halide (1mmol) and K3PO4 (2mmol), evacuated and backfilled with argon. The azole compound (1mmol) and 2mL of DMSO were added under argon. After that Cu-NP (1.6mmol) was added and the flask was again backfilled with argon. The flask was then immersed in a preheated oil bath at 80C until the conversion was completed (detected by TLC). The cooled mixture was partitioned between ethyl acetate (10mL) and saturated NH4Cl (10mL). The aqueous layer was extracted with ethyl acetate (2×10mL), the organic layer was washed with brine (20mL), dried over anhydrous Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography on silica gel using ethyl acetate in hexane (1.5-10%) as eluent to afford the desired product. All the products have been characterized by 1H NMR, 13C NMR, and mass spectroscopy. For new products, FTIR data were also recorded.
70%
With copper(I) oxide; potassium phosphate; tetrabutylammomium bromide; In water; at 130℃; for 24h;Closed system;
General procedure for N-arylation of amines:The N-nucleophile (1.47 mmol), Cu2O (Sigma-Aldrich, 99.99% purity, 0.147 mmol), K3PO4 (2.94 mmol), the aryl halide (1.76 mmol), phase transfer catalyst (0.147 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 130 C for 24 h, then the heterogeneous mixture was cooled to RT and diluted with dichloromethane. The resulting solution was directly filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of all products was confirmed by 1H and 13C NMR spectroscopic analysis.
With rhodium(III) chloride trihydrate; hydrogen; triethylamine; triphenylphosphine; In N,N-dimethyl acetamide; at 90℃; under 7500.75 Torr; for 12h;Autoclave;
General procedure: All reactions were carried out in an 80 mL Teflon-lined stainless steel reactor equipped with a magnetic stirring bar. Typically, in a glovebox, the aryl iodides (1.0 mmol), RhI3(0.025 mmol), PPh3 (0.1 mmol), Et3N (1.2 mmol), and DMA (2 mL) were loaded into the reactor. Then, the autoclave was screwed up, charged with CO and H2 to a total pressure of 10 bar (1:1) and transferred to an oil bath preheated at 90 C, which was controlled by a Haake-D3 temperature controller. After completion of the reaction, the reactor was cooled in iced water and the gas carefully vented. The conversion and yield of the aryl iodides and arylaldehydes were determined by GC analysis using dodecane as an internal standard. For yield determination of the other products, the reaction mixture was first analyzed by GC-MS to determine the structures of the aromatic aldehyde products. Then, CH2Cl2 (5 mL) was added to the reaction mixture, after which deionized water (10 mL) was added to extract the solvent DMA for 5 times. The organic layer was dried over anhydrous Na2SO4, concentrated by rotary evaporation and finally purified by column chromatography on silica gel using n-hexane/ethyl acetate as eluent to obtain the pure products and isolated yields.
With oxone; In water; acetonitrile; at 20℃; for 12h;
General procedure: Method a: A mixture of iodoarene 1a-o (1 mmol) and Oxone (2.46 g, 4 mmol) in 4 ml H2O-MeCN solution (3 : 1 v/v) was vigorously stirred until full conversion of substrate. The resulting mixture was poured into 20 ml of water and the precipitate was filtered. The obtained white solids were washed by water (3 x 10 ml) and organic solvent (1 x 10 ml) and dried in vacuum. Most products are partially soluble in water. Method b (Scale-up): The products 2a, 2d, 2e, 2i and 2o were also prepared in a larger scale using 10 mmol of iodoarene.
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triphenylphosphine; In tetrahydrofuran; at 20℃;
Chloro-3-iodobenzene (10.0 g, 41.9 mmol) was dissolved in 100 mL dry THF and 17.5 mL triethyl amine. This mixture was evacuated and backfilled with argon several times to remove oxygen from the solution. Triphenylphosphine (329 mg, 1.25 mmol) and bis(triphenylphosphine)palladium(II)chloride (1.47 g, 2.09 mmol) were added and the reaction mixture was stirred at room temperature for 1 h. Copper(I)iodide (239 mg, 1.25 mmol) and trimethylsilylacetylen (6.28 g, 6.39 mmol) were added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated. The residue was taken up in 500 mL water and extracted three times with ethyl acetate (500 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by flash-chromatography on silica gel (heptane/ethyl acetate 100:0->80:20 gradient). The desired product was obtained as a light yellow oil (7.38 g, purity 70%, yield 59%)
With potassium fluoride; iodine; In 1,4-dioxane; at 80℃; for 1h;
General procedure: A mixture of the arylboronic acid (0.55mmol), KF (96mg, 1.65mmol) and I2 (127mg, 0.50mmol) in 1,4-dioxane (5mL) was stirred at 80C for 1h. Then it was filtered through silica gel, eluting with Et2O (10mL) and the solvent was removed by rotary evaporation. When necessary, the product was purified by chromatography on silica gel (petroleum ether/Et2O 98:2).
73%
With iodine; potassium carbonate; In acetonitrile; at 80℃; for 9h;Inert atmosphere; Schlenk technique; Sealed tube;
General procedure: Arylboronic acid 1 (0.5 mmol) and K2CO3 (1 mmol, 138.0mg) were added to a 20 mL Schlenk-tube equipped with amagnetic stir bar. The tube was evacuated twice and backfilledwith N2. MeCN (2 mL) and I2 (0.75 mmol, 191 mg)were added to the tube at r.t. under a stream of N2, and thetube was sealed and placed into a pre-heated oil bath at 80 Cfor 8-12 h. The resulting solution was cooled to r.t. and H2O(10 mL) was added. The aq layer was extracted with EtOAc (3 × 5 mL). For products 2s and 2t, HCl (1 M) was added tothe aq solution until pH 2 before extraction. The combinedorganic phase was dried over anhydrous Na2SO4, filteredand concentrated by rotary evaporation. Purification of theresidue by column chromatography on silica gel providedthe desired product 2a-v
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); copper (I) iodide; triethylamine; at 20℃;Inert atmosphere;
General procedure: A round-bottomed flask containing a magentic stirbar and iodobenzene (911.5 mg, 4.468 mmol,1.0 equiv) was added with PdCl2(PPh3)2 (62.9 mg, 0.0896 mmol, 0.02 equiv), CuI (34.9 mg, 0.183mmol, 0.04 equiv) and 5.0 mL of Et3N. The resulted mixture was thoroughly degassed by a steadystream of argon for 15 min before propargyl alcohol (0.14 mL, 270.2 mg, 4.820 mmol, 1.1 equiv)was added via syringe. Ther resulted reaction mixture was allowed to stir at room temperatureunder argon overnight. The reaction mixture was diluted with saturated aqueous NH4Cl and theseparated aqueous layer was extracted with 3xEtOAc. Combined organic phases were washed withsaturated aqueous NaCl, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to givea crude material. The crude material was purified by SiO2 column chromatography eluting with10% EtOAc-hexane to give the desired product 1a as a brown oil (451.5 mg, 76%);.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 30℃; for 1h;Inert atmosphere; Sealed tube;
General procedure: For example, synthesis of 1,2-diphenylethyne, 3a. To an oven-dried 5 mL microwave vessel was added Pd(PPh3)2Cl2 (3.5 mg, 0.005 mmol, 2 mol %) and CuI (1.9 mg, 0.01 mmol, 4 mol %). The vessel was then capped and purged with N2 before addition of Cyrene (0.5 mL, 0.5 M), Et3N (38 muL, 0.275 mmol, 1.1 equiv), iodobenzene (27.9 muL, 0.25 mmol, 1 equiv), and phenylacetylene (28.8 muL, 0.263 mmol, 1.05 equiv). The reaction mixture was heated to 30 C and maintained at this temperature with stirring for 1 h before the vessel was vented, and decapped. The solution was then diluted with EtOAc (10 mL), and washed with water (2× 20 mL) and brine (2 × 20 mL). The organics were then passed through a hydrophobic frit and concentrated under reduced pressure to give a yellow oil, which was purified by flash chromatography (silica gel, 0-5% Et2O in petroleum ether) to afford the title compound as a white solid (44.5 mg, quant.).
80%
With triethylamine; In water; at 80℃; for 21h;
General procedure: A 10 mL round-bottom flask was charged with iodobenzene (4a, 1 mmol, 1 eq.), phenylacetylene (7a, 1.5mmol, 1.5 eq.), triethylamine (3 mmol, 3 eq.), H2O (2 mL), and Pd catalyst (0.01 mmol). The flask was stirred at 80C in air. The reaction was monitored by TLC and GC. After the reaction was complete, the reaction mixture was cooled to room temperature and ethyl acetate (5mL) was added to the flask. Afterward, the catalyst was filtered and washed with water (10 mL) and ethyl acetate (10 mL). The aqueous phase was extracted three times with 30 mL EtOAc. The organic phases were collected together, dried over MgSO4, and filtered. The solvent was then evaporated under reduced pressure. The pure product was obtained via silica gel column chromatography with an eluent of EtOAc and hexane. The resulting product was analyzed by 1H NMR spectroscopy.
General procedure: A 10 mL round-bottom flask was charged with iodobenzene (4a, 1 mmol, 1 eq.), butyl acrylate (5, 1.5 mmol, 1.5 eq.), tributylamine (3 mmol, 3 eq.), H2O (2 mL), and Pd catalyst (0.01 mmol). The flask was stirred at 90 C in air. The reaction was monitored by thin layer chromatography (TLC) and gas chromatography (GC). After the reaction was complete, the reaction mixture was cooled to room temperature and then simply filtered to recover the catalyst. It was then washed with 10mL of H2O and ethyl acetate (EtOAc). The organic phase was separated from the aqueous phase, which was extracted three times with 30 mL EtOAc. The organic phases were collected together, dried over MgSO4, and filtered. The solvent was then evaporated under reduced pressure. Pure product was obtained via silica gel column chromatography with an eluent of EtOAc and hexane. The resulting product was analyzed by 1H NMR spectroscopy.
100%Chromat.
With porous chitosan microspheres supported palladium catalyst; In ethylene glycol; dimethyl sulfoxide; at 110℃; for 5h;
General procedure: To a 20 ml round bottom flask containing 5.0 ml DMSO, added aromatic iodide (1.0 mmol), acrylate (2.0 mmol), Pd/PCMS (0.01 mmol) and potassium acetate (7.5 mmol). The resulting solution was allowed to stir and the reaction progress was monitored by TLC and/or GC/MS analysis. After completion, the reaction mixture was cooled down, and then quenched with 10 ml of water and extracted three times with ethyl acetate (3 × 20 ml). The combined organic layer was washed with water, saturated brine, and then dried over anhydrous Na2SO4. Solvent was removed under a reduced pressure. The cross-coupling product was purified by silica gel chromatography with petroleum ether and ethyl acetate. The cross-coupling products are known and they are all consistent with the chemical structures as characterized from 1H NMR and GC/MS analysis.
With tetrabutyl-ammonium chloride; sodium hydrogencarbonate;palladium diacetate; In DMF (N,N-dimethyl-formamide); at 0 - 50℃; for 36.5h;
Tetrabutylammonium chloride (6.95 g, 0.25 mol, 1.0 eq. ) and sodium hydrogen carbonate (5.25 g, 0.625 mmol, 2.5 eq. ) were dissolved reasonably in DMF (15 mL) under nitrogen. The mixture was cooled to 0 C before 3-chloro-iodobenzene (5.96g, 3.10 mL, 0. 25 mol), then allyl alcohol (2.18g, 2.56 mL, 0.375 mol, 1.50 eq. ) and finally Pd (OAc) 2 (0.168g, 7.5 mmol, 0.03 eq. ), the latter in small portions, was added. The mixture was stirred at 0 C for 0. 5h, and finally at room temperature for 16h. TLC showed that some 3-chloro- iodobenzene remained. The reaction mixture was then heated at 50C for 5h. TLC still showed remains of 3-chloro-iodobenzene and consequently, heating at 50C was continued for another 15h. After that time DMF was evaporated under vacuum with heating at 40C for 8h. Afterwards, water (30 mL) was added and the black reaction mixture was extracted with pentane (4x30 mL). Combined pentane phases were dried with sodium sulphate and evaporated. This gave 2.487 g (yield: 59 %) of product. TLC Rf (heptane/AcOEt 4: 1) = 0. 17. 1H NMR (500 MHz): 9.81 (s, 1H), 7.24-7. 17 (m, 3H), 7.09-7. 06 (br d, 1H), 2.93 (t, J=7.5 Hz, 2H), 2. 78 (t, J=7.5 Hz, 2H). 13C NMR (75 MHz): 200.5, 142.2, 134.0, 129.6, 128.2, 126.3, 126.2, 44.8, 27.6
With tetrabutyl-ammonium chloride; sodium hydrogencarbonate;palladium diacetate; In DMF (N,N-dimethyl-formamide); at 50℃; for 16h;
3-(3-Chloro-phenyl)-propionaldehyde. A solution of. 1-chloro-3-iodobenzene (9.63 g, 40.38 mmol), allyl alcohol (5.86 g, 100.96 mmol), sodium bicarbonate (8.48 g, 100.96 mmol), tetrabutylammonium chloride (11.22 g, 40.38 mmol), and Pd(OAc)2 (317 mg, 1.413 mmol) in 25 mL DMF was stirred at 50 C. for 16 h. The mixture was cooled to room temperature, diluted with water, and the aqueous solution was washed with EtOAc. The organic solution was washed with water followed by brine, dried over MgSO4, filtered and concentrated in vacuo. The product was purified via flash chromatography on silica gel (9:1 hexanes:EtOAc) to afford the title compound as an oil (5.04 g).
methyl 1-(3-chlorophenyl)-1H-indole-7-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With caesium carbonate; copper(l) chloride; In 1-methyl-pyrrolidin-2-one; 2,2,6,6-tetramethylheptane-3,5-dione; at 120℃; for 72h;
Step 1 Methyl 1 -(3 -chlorophenyl)- 1 H- indole-7-carboxylate; A mixture of methyl lH-indole-7-carboxylate (0.175 g), 3-iodo-chlorobenzene (0.358 g), Cs2CO3 (0.490 g), CuCl (0.099 g), and 2,2,6,6-tetramethyl-3,5-heptanedione (0.04 mL) in 5 mL of N-methylpyrolidine was heated at 120 0C for 3 days. The mixture was then diluted with 50 mL of EtOAc and filtered through a pad of solica gel. The filtrate was washed with 3 x 15 mL of water and dried over Na2SO4. After filtration and concentration, the residue was purified by Combiflash eluted with a gradient of EtOAc/hexane to give 0.1 g of the title compound.IH NMR (500 MHz, Acetone-d6): delta 7.90 (d, IH), 7.58 (d, IH), 7.50-7.58 (m, 2H), 7.41-7.46 (m, 2H), 7.23 (d, IH), 7.25 (t, IH), 6.83 (s, IH).
With n-butyllithium; nitric acid In hexane; nitrogen; water; benzene
R.9 Preparation of 1-Chloro-5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrobenzene (Compound XVI)
Reference Example 9 Preparation of 1-Chloro-5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrobenzene (Compound XVI) To 10.0 g (41.9 mmol) of 1-chloro-3-iodobenzene in 50 ml of dry benzene, 32.0 ml of a n-butyllithium solution in hexane (1.56 mol/1) was added dropwise in a nitrogen stream at room temperature with stirring. After another 2 hours of stirring at room temperature, 9.9 g (42.5 mmol) of 3,5-dichloro-4-fluorobenzotrifluoride was added dropwise at 10° C. After another 12 hours of stirring at room temperature, the reaction mixture was poured into 500 ml of water for separation. The organic layer was washed with 200 ml of water twice and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Purification of the residue by silica gel column chromatography afforded 5.0 g of 1-chloro-3-(2,6-dichloro-4-trifluoromethylphenyl)benzene (yield 35.0%). To 50 ml of fuming nitric acid, 5.0 g (15.4 mmol) of 1-chloro-3-(2,6-dichloro-4-trifluoromethylphenyl)benzene was added dropwise at -30° C. After 15 minutes of stirring at the same temperature, the reaction mixture was warmed to 5° C., poured into about 200 ml of ice-cold water and extracted with 100 ml of diethyl ether twice. The diethyl ether layer was washed with 200 ml of water twice and dried over anhydrous magnesium sulfate, and the diethyl ether was distilled off under reduced pressure. Purification of the residue by silica gel column chromatography afforded 3.0 g of 1-chloro-5-(2,6-dichloro-4-trifluoromethylphenyl)-2-nitrobenzene (yield 52.6%) as a pale yellow liquid (nD20 1.5744), which was used in Example 8 (2) as the starting material.
With copper(l) iodide; manganese(II) fluoride; (1R,2R)-1,2-diaminocyclohexane; potassium hydroxide; In water; at 60℃; for 24h;
General procedure: The N-nucleophile (1.47 mmol), CuI (Sigma-Aldrich, 99.999% purity, 0.147 mmol), MnF2 (Sigma-Aldrich, 98% purity, 0.441 mmol), KOH (2.94 mmol), the aryl halide (2.21 mmol), trans-1,2-diaminocyclohexane (0.294 mmol) and water (0.75 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 60C for 24 h. After cooling to room temperature, the mixture was diluted with dichloromethane and filtered through a pad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by silica-gel column chromatography to afford the N-arylated product. The identity and purity of known products was confirmed by 1H and 13C NMR spectroscopic analysis.
75.3%
With (E)-2-hydroxylbenzaldehyde oxime; potassium carbonate;copper(I) oxide; In N,N-dimethyl-formamide; at 95℃; for 16h;
A mixture of pyrazole (5.8 g, 84.8 mmol), potassium carbonate (15.6 g, 113.0 mmol), cuprous oxide (404 mg), salicylaldoxime (1.55 g), 3-chloroiodobenzene (7.0 mL, 56.5 mmol) and N,N-dimethylformamide (20 mL) was stirred under a nitrogen atmosphere at 95 C. for 16 hours. The reaction solution was allowed to cool to room temperature. Then water was added thereto and the mixture was extracted with toluene. The organic phases obtained were combined and concentrated. The residue obtained was purified by silica gel column chromatography, to give 1-(3-chlorophenyl)pyrazole as a pale yellow oily substance (7.6 g). Yield: 75.3%. 1H-NMR (200 MHz, CDCl3) delta: 6.48 (t, J=1.8 Hz, 1H), 7.25 (br d, J=8.0 Hz, 1H), 7.37 (t, J=8.0 Hz, 1H), 7.58 (br d, 8.0 Hz, 1H), 7.68-7.80 (m, 2H), and 7.91 (d, J=2.6 Hz, 1H).
15%
With 2,2'-biimidazole; copper(II) acetate monohydrate; caesium carbonate; In dimethyl sulfoxide; at 80℃; for 48h;
(1) m-chloroiodobenzene 0.238g (1.0mmol), pyrazole 0.069g (1.0mmol), Cu (OAc)2·H2O 0.030g (0.15mmol), 2,2- bipyridine 0.024g (0.15mmol), cesium carbonate 0.652g (2mmol), DMSO (2mL) was added the reaction tube with a piston, was heated to 80 deg.] C with stirring for 48 hours reaction.(2) TLC until the reaction was complete the reaction was followed ends.After the reaction was cooled to room temperature, diluted with water, extracted with ethyl acetate 3-4 was added, and the combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product.After the end of (3) to obtain the crude product was purified by column chromatography (petroleum ether / ethyl acetate elution) to give the desired product 8 (15% yield).
With potassium carbonate; N,N`-dimethylethylenediamine; In toluene; at 110℃; for 48h;Schlenk technique; Inert atmosphere;
General procedure: An oven-dried Schlenk tube was charged with benzamide 1 (0.5 mmol), K2CO3 (207 mg, 1.5 mmol) and aryl iodide 2 (1.0 mol). The tube was evacuated and backfilled with N2 (3 ×), and then DMEDA (0.2 mmol) and anhyd toluene (5.0 mL) were added. The reaction mixture was stirred at 110 C for 48 h. H2O was added and the crude product was extracted with EtOAc. The combined organic phases were washed with brine and H2O, dried (Na2SO4), and concentrated under reduced pressure. The product was purified by silica gel chromatographyto give the desired N-arylated benzamides (Table 2).
With copper(I) oxide; 2-(N,N-dimethylamino)athanol; water; potassium hydroxide; In dimethyl sulfoxide; at 110℃; for 24h;Inert atmosphere;
General procedure: To a test tube containing a magnetic bar was added aryl halide (1.0 mmol), Cu2O (14.3 mg, 0.1 mmol), KOH (169 mg, 3.0 mmol), 2-dimethylaminoethanol (0.3 mL, 3.0 mmol), and DMSO/H2O (1.5 mL/0.5 mL). After flushing with argon, the mixture was stirred in a preheated oil bath at 100 C for 24 h. After cooled to ambient temperature, the reaction mixture was distributed in aqueous HCl (5 %) and ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous MgSO4, and concentrated under vacuum. The crude product was further purified by column chromatography (EtOAc/n-Hexane) to provide the phenols.
88%
With tetra(n-butyl)ammonium hydroxide; In water; dimethyl sulfoxide; at 165℃; for 0.0833333h;Flow reactor;
General procedure: A solution of 4-iodotoluene (1.05 g, 4.83 mmol) in a mix of 19.3 mL of n-Bu4NOH 1.5 M aqueous solution and 19.3 mL of DMSO (for an overall 0.125 M solution vs 4-iodotoluene) was prepared. Using Flow commander software, a continuous flow experiment was designed in order to control the flow stream of the pump matching 20 min of residence time (the flow stream was set at 0.50 mL/min). 37 mL of the reaction solution was injected (corresponding to 4.63 mmol of 4-iodotoluene that will be used to calculate the isolated yield; this method being used in order to maximise the reproducibility for the reported yield)using direct injection mode and the reagent stream was pumped into the 10 mL copper reactor (1.0 mm i.d.) at 150 C. 2 X 8 bar back pressure regulators (BPR) were placed in series atthe end of the reactor, allowing safe heating of the solvent. 48 mL of the crude reaction solution was then collected into 100 mL glass vial. A reconditioning, consisting of 3 mL of DMF followed by 3 mL of a 10% aqueous acetic acid solution, was run after the experiment in order to clean the reactor. The crude reaction solution was then acidified to pH = 1 with 2 N HCl. Water (150 mL) was added and the mixture was extracted with Et2O (3 X 150 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under vacuum. The crude mixture was purified by automated flash column chromatography using a 24 g column and a 30-80% DCM/Hexanes gradient affording 406 mg of 2a (81% yield).
75%
With copper(I) oxide; caesium carbonate; toluene-4-sulfonic acid; In water; at 120℃; for 24h;Sealed tube;
General procedure: A mixture of Cu2O (Sigma-Aldrich, 99.99% purity, 0.147 mmol), Cs2CO3 (2.94 mmol),distilled water (0.2 mL), aryl halide (1.47 mmol) and p-toluenesulfonic acid (TsOH) solution(0.3 mL, 2.45 mol/dm3) were added to a reaction vial and a screw cap was fitted to it. Thereaction mixture was stirred under air in a closed system at 120 C for 24 h, following whichthe heterogeneous mixture was cooled to room temperature and diluted with dichloromethane.The combined organic extracts were dried with anhydrous Na2SO4 and the solvent wasremoved under reduced pressure. The crude product loaded into the column using minimalamounts of dichloromethane and was purified by silica-gel column chromatography to affordthe N-arylated product. The identity and purity of products was confirmed by 1H and 13CNMR spectroscopic analysis.
With oxalic acid hydrazide; ammonium hydroxide; tetrabutylammomium bromide; potassium carbonate; 2,5-hexanedione; copper(II) oxide; In water; at 90℃; for 1h;
General procedure: Under heating conditions: A 10 mL of vessel was charged with CuO (4 mg, 0.05 mmol)/CuSO4 (13 mg, 0.05 mmol), oxalyldihydrazide (24 mg, 0.2 mmol), hexane-2,5-dione (57 mg, 0.5 mmol) or 3-methylbutan-2-one (86 mg, 1.0 mmol), TBAB (81 mg, 0.25 mmol), aryl halide (1 mmol), commercial 28% aqueous ammonia (6 mmol), K2CO3(276 mg, 2 mmol) or KOH(112 mg, 2 mmol), H2O(1.0 mL). The vessel was sealed with a septum and placed into an oil bath, which was pre-heated to 90 C. The reaction mixture was stirred for 80 min at this temperature. After cooling to room temperature, the reaction mixture was extracted with ethyl acetate. The combined organic phases were washed with water and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residual oil was purified by column chromatography on silica gel (eluting with petroleum ether/ethyl acetate) to afford the desired products.At room temperature: A 10 mL of vessel was charged with CuSO4 (13 mg, 0.05 mmol, for aryl iodides) or CuO (8 mg, 0.10 mmol, for aryl bromides), oxalyldihydrazide (24 mg, 0.2 mmol or 59 mg, 0.5 mmol), hexane-2,5-dione(57 mg, 0.5 mmol or 114 mg, 1.0 mmol), TBAB (81 mg, 0.25 mmol), aryl halide (1 mmol), commercial 28% aqueous ammonia (1 mL), KOH(112 mg, 2 mmol), H2O(1.0 mL). The vessel was sealed with a septum and the reaction mixture was stirred at room temperature for 24 h (for aryl iodides) or 72 h (for aryl bromides). Then the reaction mixture was extracted with ethyl acetate. The combined organic phases was washed with water and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue oil was purified by column chromatography on silica gel (eluting with petroleum ether/ethyl acetate) to afford the desired products.
79%
With ammonium hydroxide; diethylenetriaminopentaacetic acid; copper(l) chloride; potassium hydroxide; In water; at 100℃; for 6h;Sealed tube;
238mg (1mmol) of 3-chloroiodobenzene, 1mL aqueous ammonia (25-28%, 13.3mmol), 10mg (0.1mmol) CuCl, 79mg (0.2mmol) diethylenetriaminepentaacetic acid, 112mg (2mmol) KOH, 1mL H2O was added 10mL reaction tube, sealed at 100C for 6h.After the reaction was stopped, extraction with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated under reduced pressure, purified by silica gel column chromatography purification, 3-chloroaniline was 101mg.The yield was 79%
76%
With acetamidine hydrochloride; caesium carbonate; In N,N-dimethyl-formamide; at 130℃; for 20h;Inert atmosphere; Green chemistry;
General procedure: A two-necked flask equipped with a magnetic stirring bar was charged with Cs2CO3 (2 or 3 mmol), MCM-41-L-proline-CuI (0.1 mmol), aryl iodide (1.0 mmol), acetamidine hydrochloride (1.2 or 2 mmol) and DMF (3.0 mL) under Ar. The reaction mixture was stirred at 130 or 140 C for 20 h. After being cooled to room temperature, the mixture was diluted with CH2Cl2 (10 mL) and filtered. The catalyst was washed with distilled water (2 × 5 mL) and EtOH (2 × 5 mL) and air dried when reused in the next run. The filtrate was concentrated with the aid of a rotary evaporator and the residue was purified by column chromatography on silica gel using petroleum ether (30-60 C)/ethylacetate (10:1 to 1:1) as eluent to give the desired product 2. All the products 2a-z are known compounds.
With copper(I) oxide; potassium phosphate; tetra-n-propylammonium bromide In water at 130℃; for 24h;
General procedure for N-arylation of amides
The N-nucleophile (2.21 mmol), Cu2O (Sigma-Aldrich, 99.99% purity, 0.147-0.294 mmol), K3PO4(2.94 mmol), the aryl halide (1.47 mmol), phase transfer catalyst (0.147-0.294 mmol) and water(0.40 mL) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture wasstirred under air in a closed system at 130°C for 24 h, then the heterogeneous mixture was cooledto RT and diluted with dichloromethane. The resulting solution was directly filtered through apad of Celite. The combined organic extracts were dried with anhydrous Na2SO4 and the solventwas removed under reduced pressure. The crude product was purified by silica-gel columnchromatography to afford the N-arylated product. The identity and purity of all products wasconfirmed by 1H and 13C NMR spectroscopic analysis.
With palladium diacetate; potassium carbonate; at 100℃; under 5250.53 Torr; for 3h;Catalytic behavior;
General procedure: In a typical experiment, the catalyst precursor (Pd(OAc)2, if otherwise not stated: 0.280mg, 0.00125mmol), 0.5mmol of iodoaromatic compounds, 0.625mmol (1.5 equiv.) of O-nucleophile were dissolved in 2.5mL of solvent followed by addition of 1.25mmol (2.5 equiv.) of base. The reaction mixture was placed in a glass inlet tube into a 25mL Parr Hastelloy-C high-pressure reactor equipped with manometer, safety relief, thermometer and a magnetic stirrer. The reactor was flushed with 10bar of CO three times and placed into a pre-heated oil bath at the given temperature. The final pressure was adjusted at the elevated temperature. The reaction mixture was then stirred for 4h. The pressure was monitored and maintained throughout the reaction. After cooling and venting of the autoclave after a given reaction time, the solution was removed and immediately analyzed by GC-FID and/or GC-MS.
With 2-Picolinic acid; potassium phosphate; copper(l) iodide; In dimethyl sulfoxide; at 89℃; for 24h;Inert atmosphere;
Example 58 [0215] To a mixture of 1 -chloro-3-iodobenzene (5.18 g, 21 .72 mmol) and <strong>[6358-06-1]5-amino-2-chlorophenol</strong> (5.33 g, 1 .71 equiv) and 2-picolinic acid (535 mg, 20molpercent) in 60 mL of anhydrous DMSO was charged sequentially with potassium phosphate (9.2 g, 2 equiv) and copper(l) iodide (414 mg, 10molpercent) under argon atmosphere. The resulting micture was stirred in an oil bath of 89 °C for 24 hrs, upon which TLC indicated a full conversion of the starting material. The reaction mixture was cooled down to room temperature and charged with water (50 mL) and 150 mL of ethyl acetate. The layers were separated and the organic phase was washed with brine (80 mL) and dried over anhydrous sodium sulfate. Upon filtration the organic phase was concentrated in vacuo to dryness. The residue was purified via silica gel comlumn chromatography (ethyl acetate in hexanes, 0-40percent) to afford the desired product as a brownish oil. 1H-NMR (400 MHz, CDCI3,): delta 7.22 (d, J = 7.2 Hz, 2H), 7.21 (t, J = 1 .6 Hz, 1 H), 7.05 (d, J = 8.0 Hz, 1 H), 7.04 (d, J = 8.0 Hz, 1 H), 6.84 (d, J = 6.0 Hz, 1 H), 6.39 (t, J = 2.0 Hz, 1 H), 4. 1 (dd, J = 1 .2, 7.2 Hz, 2H). MS (ESI): Calcd. For C12H10CI2NO (M+H)+: 254, found: 254.
[00341] Intermediate 12A. Ethyl l-(3-chlorophenyl)-lH-imidazole-4-carboxylate, 1 TFA: A mixture of l-chloro-3-iodobenzene (0.170 g, 0.714 mmol), ethyl lH-imidazole- 4-carboxylate (0.1 g, 0.714 mmol), copper(I) iodide (0.027 g, 0.143 mmol), and K2C03 (0.296 g, 2.141 mmol) in DMSO (1.427 mL) was vacuumed and back-filled with argon for three times, then capped and heated at 110 °C. After 16 h, the reaction was cooled to rt and was then diluted with EtOAc, washed with H20 followed by brine. The organic layer was then dried over Na2S04, filtered, and concentrated. The crude product was purified using silica gel chromatography to afford a white solid as the desired product (0.118 g, 66percent). MS(ESI) m/z: 251.0 (M+H)+.
With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 13h;
General procedure: F mixture of aryl halide (1.0 mmol), K4Fe(CN)6 (0.17 mmol), K2CO3 (1.0 mmol) and Pd/CuO NPs(0.024 mol %) in DMF (5.0 mL) was heated at 120C for the appropriate time. After completion of the reaction, the mixture was cooled to room temperature and the catalyst separated from the reaction mixture using centrifuge. The resultant solution was extracted with Et2O (320 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure to give the crude product. The residue was purified by recrystallization using ethanol and water. The purity of the compounds was confirmed by 1H NMR.
With sodium carbonate; In N,N-dimethyl-formamide; at 120℃; for 1h;Inert atmosphere; Green chemistry;
General procedure: A mixture of aryl halide (1.0 mmol), K4[Fe(CN)6](0.22 mmol), 0.05 g [PS-ttet-Pd(II)], and sodium carbonate(1.0 mmol) was stirred in 5 cm3 DMF at 120 C for 1 h under an argon atmosphere. To the aryl nitrile compound generated in situ was added sodium azide (1.5 mmol) and the mixture was stirred at 120 C for appropriate time. After completion of the reaction (as indicated by TLC), the catalyst was centrifuged, washed with EtOH and the residue was diluted with 35 cm3 ethyl acetate and 20 cm3 HCl(4 N) and stirred vigorously. The resultant organic layer was separated and the aqueous layer was extracted with 25 cm3 ethyl acetate. The combined organic layer was washed with 8 cm3 water and concentrated to give a crude product. Column chromatography using silica gel gave thepure product. All products were characterized by 1H NMR and melting point which were in agreement with literature
With triethylamine; In N,N-dimethyl-formamide; at 100℃; under 750.075 Torr; for 8h;Schlenk technique; Inert atmosphere;
General procedure: In a typical experiment a solution containing the palladiumcatalyst (with 6 mol Pd-content) was placed in a Schlenk-tube.Under argon, 0.2 mmol (22.5 l) iodobenzene (1), 0.5 mmol aminereagent, 0.7 mmol (100 l) triethylamine and 1 ml solvent wasadded and the atmosphere was changed to carbon monoxide. Thereaction mixture was heated with stirring in an oil bath at 100Cand was analysed by gas chromatography.
With iodine; palladium diacetate; triethylamine; triphenylphosphine; In toluene; at 40℃; for 4h;Sealed tube;
General procedure: PPh3 (1.3 mmol, 1.3 equiv), I2(1.3 mmol, 1.3 equiv) and4 cm3 toluene were added to a 20 cm3 test tube equipped witha stir bar, which was stirred for 10 min at room temperature.Then, aryl iodide 1, 4, or 5 (1 mmol), alkyne 2 (1.5 mmol,1.5 equiv), Pd(OAc)2 (3 mol%), and Et3N(5 mmol, 5 equiv)were added into the solution. At last, HCOOH (2 mmol, 2equiv) was added, and the tube was immediately sealed andstirred at 40 C for 4 h. After completion of the reaction,mixture was cooled to room temperature, filtered, and concentratedunder reduced pressure. The obtained residue waspurified by flash column chromatography on silica gel toprovide the corresponding products 3, 6, or 7.
79%
With triethylamine; dicyclohexyl-carbodiimide; In toluene; at 30℃; for 24h;Inert atmosphere;
General procedure: MCM-41-2P-Pd(OAc)2 (3 mol%) was transferred into an oven-dried reaction tube under Ar. Then aryl iodide (1.0 mmol), alkyne (2.0 mmol), formic acid (2.0 mmol), and toluene (4 mL) were added to the reaction tube. After DCC (2.0 mmol) and Et3N (2.0 mmol) were added, the tube was sealed, and the reaction mixture was stirred at 30 C for 24 h. After completion of the reaction, the reaction mixture was diluted with ethyl acetate (10 mL) and filtered. The catalyst was washed with DMF (2 × 5 mL), distilled water (2 × 5 mL), ethanol (2 × 5 mL), and dried at 80 C in vacuo for 1 h and reused in the next run. The filtrate was concentrated under vacuum and the residue was purified by chromatography on silica gel (eluent: light petroleum ether/ethyl acetate = 19:1) to afford the alkynyl ketone product 3.
With palladium diacetate; sodium carbonate; In water; at 100℃; under 760.051 Torr; for 8h;Sealed tube; Autoclave; Green chemistry;
General procedure: A 75 mL autoclave equipped with a Teflon liner and a magnetic stirrer bar was charged with Pd(OAc)2 (4.48 mg, 2.0 × 10-2 mmol), L (46.7 mg, 4.0 × 10-2 mmol) and H2O (6 mL) and the mixture was stirred at room temperatures for 0.5 h under N2. Then iodobenzene (113 muL, 1 mmol), phenylboronic acid (134 mg, 1.1 mmol), Na2CO3(106 mg, 1 mmol), and n-decane (0.1 mL, GC internal standard) were added. Once sealed, the autoclave was purged three times with CO, and pressurized to 1 atm of CO. The reaction mixture was stirred at 100 C for 2 h. After reaction, the mixture was extracted with diethyl ether (3 × 5 mL). The combined organic layer was concentrated in vacuo and the product was purified by column chromatography. In the recycling experiment, the aqueous phase containing the catalyst was subjected to a second run by charging it with the same substrates as mentioned above, and the reaction performed under the same conditions.
2-(3-chlorophenyl)-3,4-dihydroisoquinolin-1(2H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
With copper(l) iodide; potassium carbonate In N,N-dimethyl-formamide at 80℃; for 24h; Sealed tube;
4 Synthesis of 2-(3-chlorophenyl)-3,4-dihydroisoquinolin-1(2H)-one
Example 4 Synthesis of 2-(3-chlorophenyl)-3,4-dihydroisoquinolin-1(2H)-one In a pressure tube was charged with 3,4-dihydroisoquinolin-1(2H)-one (150 mg, 1.0 mmol), 1-chloro-3-iodobenzene (0.25 mL, 2.0 mmol), CuI (38.1 mg, 0.2 mmol), K2CO3 (152 mg, 1.1 mmol) and N,N-dimethylformamide (2 mL). The mixture was stirred at 80° C. for 24 hours, The reaction mixture was diluted with ethyl acetate and washed with HCl (2N), NH3 (10%) twice, and brine. The organic phase was concentrated, and the residue was purified on silica gel (24 g), eluted with a gradient of ethyl acetate and hexanes from 1:9 to 3:7 to give 2-(3-chlorophenyl)-3,4-dihydroisoquinolin-1(2H)-one compound as a white solid (200 mg, 76%). 1H NMR (300 MHz, CDCl3): δ 8.11-8.06 (m, 1H), 7.45-7.12 (m, 7H), 3.92 (t, J=6.4 Hz, 2H), 3.08 (t, J=6.4 Hz, 2H); Calculated for C15H12ClNO, 257.06; observed MS (ESI) (m/z) 258.1 (M+1)+.
With water; potassium carbonate; In acetonitrile; at 100℃; under 3750.38 Torr; for 0.0161111h;
General procedure: A 25 mM solution of iodobenzene (5a) and K2CO3 (2 equiv) in H2O/CH3CN (2:1) was pumped at a flow rate of 1.0 mL/min(contact time: 58 s) through a Phoenix flow reactor systemequipped with two cartridges of 4 (total 500 mg; 0.084 mmolPd). Flow hydroxycarbonylation with CO gas introduced from agas module (10 mL/min) was conducted at 100 C and a systempressure of 5 bar. The resulting solution was collected for 50min (50 mL) and the solvent was removed by evaporation. 2 Naq HCl (10 mL) was added and the resulting solid was collectedby filtration, washed with H2O (3 × 10 mL), and dried undervacuum to give benzoic acid (9a) as a white solid without anyfurther purification.Yield: 125 mg (82%); mp 122 C; 1H NMR(400 MHz, DMSO-d6): delta = 12.96 (br s, 1 H, COOH), 7.93 (d, J = 7.2Hz, 2 H, PhH-2 and PhH-6), 7.62 (t, J = 7.2 Hz, 1 H, PhH-4), 7.49 (t, J =7.2 Hz, 2 H, PhH-3 and PhH-5); 13C NMR (101 MHz, DMSO-d6): delta = 167.32 (COOH), 132.87 (Ph), 130.76 (Ph), 129.26 (Ph),128.57 (Ph); ESI-TOF-MS (neg.): m/z = 121 [M - H]-.
With dichloro bis(acetonitrile) palladium(II); cesium fluoride; In 1-methyl-pyrrolidin-2-one; at 80℃; under 760.051 Torr; for 6h;
General procedure: A mixture of aryl silane (0.5 mmol), aryl iodines (0.5 mmol), PdCl2(MeCN)2 (5 mol%), and CsF (0.5 mmol) was stirred at 80oC for 6 h in NMP (5 mL) under CO (1atm). Afterwards, 2 mL water was added to the reaction solution and then filtered through a filter paper and the solution was extracted by Et2O (2 mL) for three times. The organic phase was combined and evaporated under reduced pressure. The residue was purified on a SiO2 column to afford the desired product (ethyl acetate/hexane).
With potassium phosphate; silver(I) acetate; palladium diacetate; trifluoroacetic acid; In 1,2-dichloro-ethane; at 80 - 90℃;
Example 43-chloro -2 the same-acetamido [...] synthesis ofTo 10 ml reaction flask by adding 3-bromo(acetylaniline) (0.2mmol, 42 . 81 mg), palladium acetate (0.002mmol, 0 . 45 mg), 3- chloroiodobenzene (0.22mmol, 52 . 46 mg), K3PO4(0.6mmol, 127 . 36 mg), silver acetate (0.3mmol, 50 . 07 mg), TFA (0.1mmol) and DCE (2 ml), for 90 C reaction under the conditions, the TLC reaction monitoring, when the temperature is reduced to the room temperature, adding phenylo boric acid (1.2mmol, 29 . 26 mg) with the ligand two phenol (0.004mmol, 1 . 07 mg), 80 C to continue reaction, the end point of the detection reaction TLC. When the reaction to room temperature, add 5 ml ethyl ether, the reaction solution is poured into the separatory funnel, using 5 ml ethyl ether washing reaction bottle, and then merged into the separatory funnel in ethyl ether, is added to the separatory funnel in 10 ml saturated NaCl solution, oscillating, liquid, so then to 10 ml × 2 of ethyl ether extraction, combined with the phase, adding anhydrous sodium sulfate for drying, filtering, vacuum screwed out of the solvent, with petroleum ether and ethyl acetate 3:1(v/v) as the mobile phase, rapid column separation, get the pure product white solid 3-chloro -2 the three-acetamido [...] biphenyl, yield 86.5%.
With potassium phosphate; copper; In dimethyl sulfoxide; at 100℃; for 24h;
General procedure: A mixture of Cu0 powder (Sigma-Aldrich, <425mum, 99.5% trace metals basis, 0.095mg, 0.015mmol, 3-mol%), anhydrous K3PO4 (0.75mmol), <strong>[872-35-5]2-mercaptoimidazole</strong>/sulfur-containing azoles (0.5mmol), DMSO (0.2mL) and aryl halide (0.75mmol) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 100C for 24h. The heterogeneous mixture was subsequently cooled to room temperature and diluted with 4.0mL dichloromethane. The combined organic extracts were dried with anhydrous Na2SO4, filtered and the solvent was removed under reduced pressure. The crude product was loaded onto the column using minimal amounts of dichloromethane and was purified by silica-gel column chromatography to afford the S-arylated product. The identity and purity of products was confirmed by 1H and 13C NMR spectroscopic analys.
With pyridine; cesium fluoride; In dimethyl sulfoxide; at 105℃; for 2h;Inert atmosphere; Schlenk technique;
General procedure: An oven-dried Schlenk tube, containing a Teflon-coated magnetic stir bar was charged with CsF (228 mg, 1.5 mmol, 3 equiv) and bispinacolatodiboron (254 mg, 1 mmol, 2 equiv). Under an argon atmosphere, freshly distilled DMSO (0.4 mL), the appropriate aryl iodide (0.5mmol), and pyridine (0.4 to 1 equiv) were added successively. The reaction mixture was heated to 105 C and stirred for 2 h under argon.
Accurate weighing of m-chloroiodobenzene (3-chloroiodobenzene) (23.85 g, 0.1 mol) was dissolved in 120 ml of methyl tert-butyl ether and the ethanol cooled ice bath cooled to a negative temperature of 20 to minus 10 C. A solution of isopropylmagnesium chloride (0.13 mol) was added dropwise and incubated for 1 hour at a negative 20 to minus 10 C after completion of the dropwise addition. Then, trifluoroacetate (18.4 g, 0.13 mol) was added dropwise at this temperature. After completion of the dropwise addition, the mixture was stirred and cooled to room temperature, and then hydrochloric acid (30 ml, 0.3 mol) was added dropwise. The organic layer was removed under reduced pressure to give 20.5 g of crude 2,2,2-trifluoro-(3'-chlorophenyl)ethanone and distilled to give 18.3 g of a colorless transparent liquid, content of 95.9.7%, the yield of 88%.
With sodium t-butanolate; In tetrahydrofuran; toluene; at 50℃; for 6h;Sealed tube;
General procedure: 1-Chloro-4-iodobenzene (48 mg, 0.20 mmol), 48 mg, 0.20 mmol)1,1-Dibornathethane (2, 107 mg, 0.30 mmol) and sodium tert-butoxide base (38 mg, 0.40 mmol) were placed in a 4 mL vial. Toluene / tetrahydrofuran (2.0 mL, 1: 1 mixed solution) was then added.The vial was reacted for six hours at 80 C sealed with a PTFE / silicone coated cap.The reaction solution was filtered through celite with dichloromethane, and the organic material was concentrated under reduced pressure. The products were then separated and purified on silica gel column chromatography Phi 2.0 cm × 8 cm under the specified eluent conditions under n-hexane: diethyl ether, 10: 1 eluent. As a result 2- (4-Chlorophenyl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane boronated compound was produced. (32 mg, 67% yield); The procedure of Example 3 was followed except that aryl iodide was changed according to the following reaction formula (3), and the results are shown in Table 2.
With potassium carbonate; N,N`-dimethylethylenediamine In toluene at 110℃; for 48h; Schlenk technique; Inert atmosphere;
N-Arylated Benzamides 3
General procedure: An oven-dried Schlenk tube was charged with benzamide 1 (0.5 mmol), K2CO3 (207 mg, 1.5 mmol) and aryl iodide 2 (1.0 mol). The tube was evacuated and backfilled with N2 (3 ×), and then DMEDA (0.2 mmol) and anhyd toluene (5.0 mL) were added. The reaction mixture was stirred at 110 ° C for 48 h. H2O was added and the crude product was extracted with EtOAc. The combined organic phases were washed with brine and H2O, dried (Na2SO4), and concentrated under reduced pressure. The product was purified by silica gel chromatographyto give the desired N-arylated benzamides (Table 2).
8-(3-chlorophenyl)-1,4-dioxaspiro[4.5]dec-7-ene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
96%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 70℃; for 5.0h;
To a solution of 1-chloro-3-iodobenzene (7.14 g, 30 mmoL) in 1, 4-dioxane /H2O (80 mL/20mL) was added 4, 4, 5, 5-tetramethyl-2- (1, 4-dioxaspiro [4.5] dec-7-en-8-yl) -1, 3, 2-dioxaborolane (7.98 g, 30 mmol), Pd (dppf) Cl2 (2.19 g, 3.0 mmol) and Cs2CO3 (11.7 g, 36 mmol) and the mixture was heated at 70 for 5 hours. Then evaporated the solvent under reduced pressure and the residue was purified by column chromatography (PE: EA=5: 1) to give product as an oil (7.2 g in 96% yield). [M+H] +=251
4-(3-chlorophenyl)-3,3,4,4-tetrafluorobut-1-ene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
General procedure: In a two-necked round-bottomed flask, equipped with a teflon-coated stirrer bar, were added iodobenzene (3a, 0.40 mL, 3.6 mmol) and Cu2O (0.027 g, 0.18 mmol), and a DMF solution of 2-Zn (0.60 M, 1.0 mL, 0.6 mmol). The whole was heated up at 100 C and stirred at that temperature for 24 h. After cooling to room temperature, the resultant was filtered through a short pad of silica gel using hexane as an eluent. The filtrate was concentrated in vacuo to give the crude materials, which was purified by silica gel column chromatography using hexanes as an eluent, leading to the corresponding compound 4a (0.036 g, 0.17 mmol) in 29% isolated yield as a colorless oil.
1-(3-chlorophenyl)-1H-imidazole-4-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h;
General procedure: A solution of <strong>[57090-88-7]4-cyano-1H-imidazole</strong> (1000 mg, 10.74 mmol), 4-iodo -2-(trifluoromethyl)pyridine (3800 mg,14 mmol), (1R,2R)-N1,N2-dimethyl cyclohexane -1,2-diamine (150 mg, 1.07 mmol), CuI (200 mg, 1.07 mmol) and Cs2CO3 (7000 mg, 21.5 mmol) in 20 mL anhydrous DMF was stirred at 100 oC for 2 hours. The reaction mixture was cooled to room temperature and poured into 200 mL water. The mixture was extracted with ethyl acetate (80 mL*3). The organic layer were combined, washed by brine, dried by Na2SO4 and evaporated. The crude product was purified by silica flash column to afford compound 2 as white solid(1.5 g, 59percent yield).
diethyl dithiocarbamic acid 3-chlorophenyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With copper acetylacetonate; tetrabutylammomium bromide; sodium carbonate; In water; at 100℃; for 12h;Sealed tube;
General procedure: Aryl iodides (1.0 mmol), tetraalkylthiuram disulfides (1.0 mmol), Cu(acac)2 (0.1mmol), Na2CO3 (1.0 mmol), n-Bu4NBr (0.1 mmol) and H2O (2.0 mL) were taken in a25-ml sealed tube. The reaction mixture was stirred at 100 C for 12 hours. Aftercooling to room temperature, the product was diluted with H2O (5 mL) and extractedwith EtOAc (3×10 mL). The extracts were combined and washed by brine (3×10 mL),dried over MgSO4, filtered, and evaporated, and purified by chromatography on silicagel to obtain the desired products with ethyl acetate/hexane (v/v=1:3 1:10). Theproducts were characterized by their spectral and analytical data and compared withthose of the known compounds.
ethyl (2R)-2-[(tert-butoxy)carbonyl]amino}-5-(3-chlorophenyl)-5-oxopentanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
3.97 g
To a solution of 1-chloro-3-iodobenzene (2.89 mL) in THF (60 mL) was added dropwise isopropylmagnesium chloride (2.0 mol/L, THF) (11.6 mL) under an argon atmosphere at -40C, and the mixture was stirred at the same temperature for 15 minutes. To the reaction mixture was added dropwise a solution of ethyl (R)-1-(tert-Butoxycarbonyl)-5-oxopyrrolidine-2-carboxylate (3.0 g) in THF (20 mL) at -40C, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture were added a saturated aqueous solution of ammonium chloride and water. The mixture was stirred at room temperature for 3 hours, and then extracted twice with ethyl acetate. The combined organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=90/10-60/40) to give the title compound (3.97 g).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
