* 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] Organic Letters, 2014, vol. 16, # 6, p. 1768 - 1771
[2] Chemical Communications, 2017, vol. 53, # 33, p. 4585 - 4588
[3] Journal of Organic Chemistry, 2018, vol. 83, # 10, p. 5698 - 5706
9
[ 63069-48-7 ]
[ 140-89-6 ]
[ 51618-29-2 ]
Yield
Reaction Conditions
Operation in experiment
92.3%
With copper(l) chloride In N,N-dimethyl-formamide at 110℃; for 6 h; Inert atmosphere; Sealed tube
General procedure: A 25 mL Wattecs reaction tube was charged with 2-haloaniline 1 (0.6 mmol), potassium O-ethyl dithiocarbonate 2 (1.8 mmol),CuCl (0.06 mmol), and DMF (2 mL). The reaction vessel was flushed with argon three times and sealed. Then the mixture was stirred electromagnetically in an oil bath at 110°C for 6 h.The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, and then HCl (3 mL, 3 mol/L) was added and stirred for another 30 min. The reaction mixture solution was extracted by ethyl acetate (3 × 20 mL). Subsequently, the combined organic solutions were dried by anhydrous sodium sulfate and the target product was purified by chromatography on a silica gel column (eluent: petroleum ether/ethyl acetate) togive the corresponding pure product 3. Complete characterization characterizationof the products (all known) is found in the Supplemental Materials (Figures S1–S13).
77%
With iron(III) trifluoride; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In N,N-dimethyl-formamide at 110℃; for 18 h; Inert atmosphere; Sealed tube
General procedure: A 25 mL reaction tube was charged with 2-haloaniline 1 (0.6 mmol), potassium o-ethyldithiocarbonate 2 (1.8 mmol), FeF3 (0.06 mmol), 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl (0.03 mmol) and DMF (4 mL). The reaction vessel was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically in an oil bath at 110 for 3 - 21 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, then 4 mL HCl (3mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by ethyl acetate (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous sodium sulfate and the target product was purified by silica gel colum chromatography (eluent: petroleum ether / ethylacetate) to give the corresponding pure product 3.
Reference：
[1] Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 5, p. 699 - 701
[2] Synthetic Communications, 2015, vol. 45, # 20, p. 2378 - 2385
10
[ 75-15-0 ]
[ 63069-48-7 ]
[ 51618-29-2 ]
Yield
Reaction Conditions
Operation in experiment
82%
With sodiumsulfide nonahydrate In N,N-dimethyl-formamide at 110℃; for 12 h; Sealed tube; Inert atmosphere
General procedure: A sealed tube (50 mL) was charged with 2-haloaniline 1a (2mmol), CS2 (10 mmol), Na2S (4mmol) and DMF (2 mL) at room temperature under an argon gas atmosphere and the tube was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically at 110 °C for 12 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, 2 mL HCl (3 mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by dichloromethane (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel colum chromatography (eluent: petroleum ether / ethyl acetate) give the corresponding pure product 2a.
With hydrogenchloride; sodium iodine dichloride In methanol; water at 20℃; for 3 h;
General procedure: To a solution of the aniline (1, 20.0 mmol) in a mixture of H2O (100 mL) and MeOH(300 mL), was added conc. hydrochloric acid was added until pH was 1–2 (pH strip).Then an aqueous solution of NaICl2 (50percent w/w 1.1–4;.8 molar equiv; for amount, seeTable) was added dropwise and the resulting mixture was stirred with a stirring bar atroom temperature for 3–4 h. Saturated aqueous NaHSO3 was added until negative starchtest was obtained and the product was worked up.When no precipitate was clearly visible in the product mixture, the mixture was madeslightly basic (pH strip) by dropwise addition of an aqueous solution of NaOH (1 M) andextracted with Et2O. The combined organic phases were dried (MgSO4), filtered, and concentratedunder vacuum to give a solid.When a visible precipitate was obtained, the solid was isolated by gravity filtration(each case specified below) and the filtrate was then made slightly basic (pH strip) byaddition of an aqueous solution of NaOH (1 M) and extracted with Et2O. The combinedorganic extracts were dried (MgSO4), filtered, and concentrated under vacuum to afford asolid.All the solids were analysed by TLC (silica gel; varying mixtures of hexanes/ethylacetate). When a solid consisted of several products, the compounds were separated andpurified by flash chromatography (silica gel; hexanes/ethyl acetate 9:1 when not otherwisestated).The products obtained were characterized by mps (and comparison with lit. mps), IR,MS, 1H- and 13C-NMR spectra as well as elemental analysis for all new compounds. Theanisidines gave no products that could be characterized. Anilines 1a–1j gave products assummarized below; most of them are known from the literature.
Reference：
[1] Organic Preparations and Procedures International, 2016, vol. 48, # 5, p. 385 - 392
[2] Synlett, 2014, vol. 25, # 6, p. 831 - 834
12
[ 106-47-8 ]
[ 63069-48-7 ]
Yield
Reaction Conditions
Operation in experiment
100%
With iodine; sodium hydrogencarbonate; potassium iodide In water for 3.75 - 5.75 h;
EXAMPLE 1 Preparation of 4-chloro-2-iodoaniline An aqueous solution of potassium iodide (50 g, 0.301 mol), iodine (76 g, 0.299 mol), and water (100 mL) is added over 45 min. to a stirred suspension of 4-chloroaniline (35 g, 0.276 mol, 50 um average particle size), sodium hydrogen carbonate (37 g, 0.440 mol) and water (210 mL). The mixture is stirred for 3-5 hours. The solid is collected by filtration and washed with water, then dried to provide 4-chloro-2-iodoaniline (69.6 g, 100percent yield, 98.5percent purity). 1H NMR (CDCl3): δ 7.56 (d, 1H, J=2.4 Hz), 7.12 (dd, 1H, J=2.4 Hz, 8.6 Hz), 6.75 (d, 1H, J=8.6 Hz), 5.37 (br s, 2H).
91%
With N-iodo-succinimide; [(Ph3P)Au]NTf2 In dichloromethane; toluene at 20℃; for 14 h;
General procedure: To a stirred solution of the substrate (1 mmol) in CH2Cl2 or (CH2Cl)2 (0.1 M) were added Ph3PAuNTf2 (0.025 mmol, 19 mg; complex Ph3PAuNTf2 toluene, 2:1) followed by N-iodosuccinimide (1.1 mmol, 248 mg). The resulting solution was stirred at r.t. or under reflux until complete conversion of the starting material. After removal of the solvent under reduced pressure, the crude material was purified by flash column chromatography using different gradients of hexanes and EtOAc to obtain the pure desired products.
86%
With dipotassium peroxodisulfate; choline chloride; iodine In acetonitrile at 65℃; for 2 h;
General procedure: To a solution of aromatic compound (10 mmol) in acetonitrile (5 mL) in a 100 mL round-bottomed flask with a magnetic bar was added choline chloride(10 mmol), potassium peroxodisulfate (10 mmol) and iodine (15 mmol). The reaction mixture was stirred for the appropriate time at 65 °C. The progress of the reaction was monitored by TLC. The reaction mixture was poured into aqueous sodium thiosulfate solution (1 mol/L) in order to remove unreacted iodine and extracted with ethyl acetoacetate (10 mL, 3 times). Organic layer is dried over anhydrous sodium sulphate. Evaporation of the solvent under vacuum followed by column chromatography on silica gel gave the corresponding iodinated compounds (Scheme-I).
75%
at 80℃; for 2.5 h;
General procedure: A mixture of aromatic/heteroaromatic amine (1 mmol) and 1-butyl-3-methylpyridinium dichloroiodate (BMPDCI) (1.2 mmol) was heated to 80°C for 1-4 h. After completion of the reaction (monitored by TLC), ethyl acetate was added, followed by addition of water. The organic layer was separated and the aqueous layer was extracted three times with ethyl acetate. The combined organic layer was dried using sodium sulfate and evaporated under vacuum to afford the crude product, which on further column chromatography using silica gel afforded the pure iodinated product as shown in Table 1.
70%
With 1,4-dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate In neat (no solvent) at 20℃; for 0.416667 h;
General procedure: General procedure for the iodination of aryl amines under solvent-free conditions.DBDABCODCI (0.5 mmol) and aryl amine (1 mmol) were triturated together in a porcelainmortar at room temperature. After completing reaction which monitored by TLC, the ethylacetate added to mixture and filtered, the organic layer washed with 5percent aqueous sodiumthiosulfate, and dried over MgSO4. The solvent was removed in vacuum and the crude mixturewas purified by column chromatography using ethyl acetate and hexane mixture and analyzedby m.p. and 1H NMR spectroscopy.
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[11] Synthetic Communications, 2006, vol. 36, # 13, p. 1915 - 1917
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[13] Journal of Chemical Research, 2006, # 9, p. 575 - 576
[14] Synthetic Communications, 2008, vol. 38, # 11, p. 1792 - 1798
[15] Advanced Synthesis and Catalysis, 2010, vol. 352, # 18, p. 3355 - 3363
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[39] Synlett, 2006, # 1, p. 65 - 68
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[41] Journal of Organic Chemistry, 2002, vol. 67, # 18, p. 6395 - 6405
[42] Journal of the American Chemical Society, 2002, vol. 124, # 45, p. 13463 - 13473
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[45] Patent: US2005/70723, 2005, A1, . Location in patent: Page/Page column 5
[46] Patent: US6635657, 2003, B1,
[47] Synthetic Communications, 2008, vol. 38, # 22, p. 3894 - 3902
[48] Beilstein Journal of Organic Chemistry, 2009, vol. 5,
[49] Chemical Communications, 2012, vol. 48, # 83, p. 10346 - 10348
[50] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 5, p. 1351 - 1357
[51] Journal of Organic Chemistry, 2015, vol. 80, # 21, p. 10806 - 10816
[52] Synthesis (Germany), 2016, vol. 48, # 6, p. 855 - 864
[53] Advanced Synthesis and Catalysis, 2018, vol. 360, # 16, p. 3150 - 3156
13
[ 142-71-2 ]
[ 106-47-8 ]
[ 64-19-7 ]
[ 63069-48-7 ]
[ 88149-53-5 ]
[ 116035-66-6 ]
Yield
Reaction Conditions
Operation in experiment
35%
at 120℃; for 12.5 h;
A typical procedure was followed for one-pot synthesis of substituted 2-iodoaniline and 2-iodoacetanilide from substituted aniline. A mixture of 5 g of substituted aniline 1–6 shown inTable 1, granulated iodine (1 mol. equiv.) and copper(II) acetate(1 mol. equiv.) were stirred in 50 mL of glacial acetic for 30 min.The reaction mixture was refluxed for 12 h with constant stirring at 120 C. Then the reaction mixture was allowed to cool at room temperature. The precipitate of copper(I) iodide was removed byfiltration and the filtrate was poured into water and extracted with chloroform (3 50 mL). The combined chloroform extracts were washed with sodium hydrogen carbonate solution, sodium thiosulfate solution, distilled water and dried with anhydrous sodium sulfate.A crude semi-solid mass was obtained after removal of solvent. The crude product was purified by column chromatographyon silica gel using n-hexane/ethyl acetate as eluant (4:1) and compounds 7–24 were isolated.
Reference：
[1] Journal of Molecular Structure, 2013, vol. 1054-1055, p. 367 - 374
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; Schlenk technique
General procedure: In a typical reaction, PdCl2(PPh3)2 (88 mg, 0.125 mmol), CuI (24 mg, 0.125 mmol) and THF (5 ml) were placed in an oven-dried, 2-neck RB flask. To this suspension, 2-iodoaniline (5.47 mg, 2.5 mmol) and triethylamine (702 μl, 5.0 mmol) were added. The reaction mixture was degassed by bubbling with argon for 15 min. Phenylacetylene (300 μl, 2.75 mmol) was then added, and the reaction mixture stirred at RT. After complete consumption of the 2-iodoanilines (~2 h, by TLC), the reaction mixture was filtered through celite, and the solvent rotary evaporated to obtain the crude product which was purified by silica gel (60-120 mesh) column chromatography using ethylacetate/ hexane (1:9, v/v) as eluent to give pure 2-phenylethynylaniline, 2a (400 mg, 83percent).
76%
With sodium hydroxide In toluene at 130℃; for 72 h;
General procedure: To a stirred solution of the corresponding 2-iodoaniline (6, 1 mmol) in toluene (3 mL) under argon atmosphere were added Pd/CuO-Fe3O4 (50 mg), NaOH (400 mg, 10 mmol), and the corresponding alkyne (2, 1.5 mmol). The resulting mixture was stirred at 130 °C until the end of reaction (see Table 6). The catalyst was removed by a magnet and the resulting mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to remove the solvent. The product was purified by chromatography on silica gel (hexane/ethyl acetate) to give the corresponding compounds 7. Yields are included in Table 6. Then, to a stirred solution of 7 (1 mmol) in toluene (4 mL) was added ZnBr2 (225 mg, 1 mmol). The resulting mixture was stirred at 130 °C during 24 h. The mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to give the pure products 8 in quantitative yields. Physical and spectroscopic data for compounds 7 and 8, as well as literature for known compounds, follow.
Reference：
[1] Angewandte Chemie - International Edition, 2013, vol. 52, # 45, p. 11835 - 11839[2] Angew. Chem., 2013, vol. 125, # 45, p. 12051 - 12055,5
[3] Advanced Synthesis and Catalysis, 2010, vol. 352, # 18, p. 3355 - 3363
[4] Journal of the American Chemical Society, 2016, vol. 138, # 43, p. 14441 - 14448
[5] Tetrahedron Letters, 2014, vol. 55, # 40, p. 5495 - 5498
[6] Tetrahedron, 2012, vol. 68, # 5, p. 1393 - 1400
[7] Journal of Organic Chemistry, 2007, vol. 72, # 15, p. 5731 - 5736
[8] Organic Letters, 2008, vol. 10, # 21, p. 4718 - 4721
[9] Journal of Organic Chemistry, 2010, vol. 75, # 21, p. 7502 - 7504
[10] Tetrahedron Letters, 2013, vol. 54, # 19, p. 2357 - 2361
[11] Organic Letters, 2013, vol. 15, # 14, p. 3710 - 3713
[12] Journal of Organic Chemistry, 2013, vol. 78, # 20, p. 10319 - 10328
[13] Organic Letters, 2013, vol. 15, # 23, p. 5940 - 5943
[14] Chemical Communications, 2014, vol. 50, # 23, p. 3024 - 3026
[15] RSC Advances, 2014, vol. 40, # 78, p. 41561 - 41564
[16] RSC Advances, 2014, vol. 4, # 78, p. 41561 - 41564
[17] Chemistry - A European Journal, 2015, vol. 21, # 8, p. 3193 - 3197
[18] Journal of Organic Chemistry, 2016, vol. 81, # 10, p. 3994 - 4001
[19] Advanced Synthesis and Catalysis, 2017, vol. 359, # 8, p. 1373 - 1378
[20] Advanced Synthesis and Catalysis, 2017, vol. 359, # 11, p. 1844 - 1848
[21] Advanced Synthesis and Catalysis, 2018, vol. 360, # 21, p. 4054 - 4059
[22] Chemical Communications, 2017, vol. 53, # 64, p. 8980 - 8983
[23] Journal of Organic Chemistry, 2017, vol. 82, # 16, p. 8455 - 8463
[24] Organic and Biomolecular Chemistry, 2017, vol. 15, # 33, p. 6997 - 7007
[25] Advanced Synthesis and Catalysis, 2018, vol. 360, # 18, p. 3460 - 3465
[26] Organic Letters, 2018,
[27] Journal of Chemical Research, 2018, vol. 42, # 11, p. 558 - 563
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 20℃;Inert atmosphere; Schlenk technique;
General procedure: In a typical reaction, PdCl2(PPh3)2 (88 mg, 0.125 mmol), CuI (24 mg, 0.125 mmol) and THF (5 ml) were placed in an oven-dried, 2-neck RB flask. To this suspension, 2-iodoaniline (5.47 mg, 2.5 mmol) and triethylamine (702 mul, 5.0 mmol) were added. The reaction mixture was degassed by bubbling with argon for 15 min. Phenylacetylene (300 mul, 2.75 mmol) was then added, and the reaction mixture stirred at RT. After complete consumption of the 2-iodoanilines (~2 h, by TLC), the reaction mixture was filtered through celite, and the solvent rotary evaporated to obtain the crude product which was purified by silica gel (60-120 mesh) column chromatography using ethylacetate/ hexane (1:9, v/v) as eluent to give pure 2-phenylethynylaniline, 2a (400 mg, 83%).
76%
With sodium hydroxide; In toluene; at 130℃; for 72h;
General procedure: To a stirred solution of the corresponding 2-iodoaniline (6, 1 mmol) in toluene (3 mL) under argon atmosphere were added Pd/CuO-Fe3O4 (50 mg), NaOH (400 mg, 10 mmol), and the corresponding alkyne (2, 1.5 mmol). The resulting mixture was stirred at 130 C until the end of reaction (see Table 6). The catalyst was removed by a magnet and the resulting mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to remove the solvent. The product was purified by chromatography on silica gel (hexane/ethyl acetate) to give the corresponding compounds 7. Yields are included in Table 6. Then, to a stirred solution of 7 (1 mmol) in toluene (4 mL) was added ZnBr2 (225 mg, 1 mmol). The resulting mixture was stirred at 130 C during 24 h. The mixture was quenched with water and extracted with EtOAc. The organic phases were dried over MgSO4, followed by evaporation under reduced pressure to give the pure products 8 in quantitative yields. Physical and spectroscopic data for compounds 7 and 8, as well as literature for known compounds, follow.
With palladium/copper catalyst;Inert atmosphere;
General procedure: All reagents were used as received without further purification.2-Alkynylanilines 1a-i were prepared by palladium/copper-catalysedSonogashira coupling reactions of 2-iodoanilines with terminalalkynes according to a literature method.31 The Fe3O4SiO2-bipy-AuCl3 complex was prepared according to our previous procedure.42The gold content was determined to be 0.62 mmol g-1. All reactionswere carried out under Ar in oven-dried glassware with magneticstirring. 1H NMR spectra were recorded on a Bruker Avance 400 (at400 MHz) spectrometer with TMS as an internal standard using CDCl3as the solvent. 13C NMR spectra were recorded on a Bruker Avance 400(at 100 MHz) spectrometer using CDCl3 as the solvent. HRMS spectrawere recorded on a quadrupole-time of flight Bruker MicroTOF-QII mass spectrometer equipped with an ESI and APCI source. Goldcontent was determined using ICP-AES on an Atomscan16 instrument(TJA Corporation).
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; for 1h;Product distribution / selectivity;
Step A: Preparation of l -Bromo-4-chloro-2-iodobcnzenc; |0892 ] A stirred mixture of coppcr(l l) bromide ( 1 1 mL, 237 mmol) in250 mL ACN at O0C was slowly treated with tert-butyl nitrite (33 mL, 276 mmol). The mixture was then warmed to 65C. and stirred for 30 minutes. The mixture was next treated dropwise with a mixture of 4-chloro-2-iodoaniline (50 g, 197 mmol) in 100 mL ACN. The resulting mixture was stirred for 1 hour. The mixture was cooled to room temperature and poured over 200 mL ice/10%HCl. The mixture was extracted with ether (3 x 100 mL). The <n="202"/>combined organic layers were washed with I hO (2 100 m l .). 1 % ammonia water (2 x 100 niL), brine ( 100 ml), dried over anhydrous Na2SOi. and concentrated in vacuo to give 63 g brown oil as crude product. The crude product was purified by running it through a short silica plug eluting with 5% ether / hexane to give 54.2 g of the title compound as a yellow solid.
With diethylamine In N,N-dimethyl-formamide at 0 - 20℃;
8.3
To a solution of 4-chloro-2-iodoaniline 8-d (2.0 g, 7.89 mmol) in DMF cooled to 0 °C was sequentially added diethylamine (5 mL, 22.83 mmol), copper (I) iodide (301 mg, 1 .57 mmol) and dichlorobis(triphenylphosphine) palladium (II) (554 mg, 0.78 mmol). After complete dissolution of copper (I) iodide, methyl hex-5-ynoate ( 1 .09 g, 8.68 mmol) was added dropwise at 0 °C and the reaction was then stirred at room temperature overnight. Water and ethyl acetate were added; the organic layer was separated, washed with saturated aqueous ammonium chloride and brine, dried over anhydrous MgSC>4, filtered and concentrated in vacuo. Purification by silica gel chromatography provided intermediate 8-e as a beige solid. MS (m/z) M+H= 252.2
With copper(l) iodide; diethylamine In N,N-dimethyl-formamide at 0 - 20℃;
3
To a solution of 4-chloro-2-iodoaniline 8-d (2.0 g, 7.89 mmol) in DMF cooled to 0 °C was sequentially added diethylamine (5 mL, 22.83 mmol), copper (I) iodide (301 mg, 1.57 mmol) and dichlorobis(triphenylphosphine) palladium (II) (554 mg, 0.78 mmol). After complete dissolution of copper (I) iodide, methyl hex-5-ynoate (1.09 g, 8.68 mmol) was added dropwise at 0 °C and the reaction was then stirred at room temperature overnight.Water and ethyl acetate were added; the organic layer was separated, washed with saturated aqueous ammonium chloride and brine, dried over anhydrous MgS04, filtered and concentrated in vacuo. Purification by silica gel chromatography provided intermediate 8-e as a beige solid. MS (m/z) M+H= 252.2
With pyridine; chloro-trimethyl-silane; triethylamine; at 100℃; for 4h;
To a suspension of 4-chloro-2-iodoaniline (0.760 g, 3 mmol) and <strong>[628-36-4]N'-formylformohydrazide</strong> (0.793 g, 9 mmol) in pyridine (12 ml) was added dropwise chlorotrimethylsilane (5.71 ml, 45 mmol) followed by TEA (2.84 ml, 20.4 mmol). The reaction mixture was heated at 100 °C. After 4 h, the reaction was cooled to rt and the reaction was concentrated to give a solid. The solid was suspended in water and the solid was collected by filtration, washing with water. The solid was air-dried and dried under vacuum to give 0.8 g as an off-white solid. Purification by normal phase chromatography afforded 0.59 g (64 percent) of Intermediate 21 A, as a white solid. MS (ESI) m/z: 306.1 (M+H)+. 3/4 NMR (400 MHz,DMSO-d6) delta ppm 7.56 (d, J = 8.2 Hz, 1 H), 7.67 (dd, J = 2.2 Hz, 8.2 Hz, 1 H), 8.17 (d, J = 2.2 Hz, 1 H), 8.78 (s, 2 H).
Stage #1: p-chloro-o-iodoaniline; phenylacetylene With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine In N,N-dimethyl acetamide at 20℃; for 1h;
Stage #2: With sodium hydroxide In N,N-dimethyl acetamide at 140℃;
Multi-step reaction with 2 steps
1: sodium hydroxide / toluene / 72 h / 130 °C
2: zinc dibromide / toluene / 24 h / 130 °C
Multi-step reaction with 2 steps
1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / 10 h / 20 - 40 °C / Inert atmosphere; Schlenk technique
2: Au/Carbon G-60 catalyst / toluene / 24 h / 90 °C / Inert atmosphere; Schlenk technique
Multi-step reaction with 2 steps
1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / tetrahydrofuran / 20 °C / Inert atmosphere; Schlenk technique
2: bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; sodium tetrafluoroborate / acetonitrile / 8 h / 40 °C / Inert atmosphere; Schlenk technique
Stage #1: p-chloro-o-iodoaniline; phenylacetylene With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diethylamine In N,N-dimethyl acetamide at 20℃;
Stage #2: With sodium hydroxide In N,N-dimethyl acetamide at 140℃;
With palladium diacetate; potassium carbonate; triphenylphosphine In ethanol at 80℃; for 5h; Inert atmosphere;
3.1.3. 5-Chloro-2-(2-furyl)aniline (2d)
General procedure: A mixture of Pd(OAc)2 (25 mg, 0.11 mmol), PPh3 (110 mg, 0.420 mmol), potassium 2-furyltrifluoroborate (420 mg, 2.40 mmol), K2CO3 (450 mg, 3.26 mmol), and 5-chloro-2-iodoaniline (1d) (400 mg, 1.60 mmol) in EtOH (96%, 100 mL) was stirred under Ar for 5 h at 80 °C. The solvent was removed in vacuo and the product purified by flash chromatography on silica gel eluting with CH2Cl2/hexane (1:4); yield 245 mg (84%), yellow oil.
(6-chloro-1,3-benzothiazol-2-yl)methylamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With 1,1'-bis-(diphenylphosphino)ferrocene; calcium oxide; In acetonitrile; at 60℃; for 8h;Inert atmosphere;
To a mixture of tert-butyl-2-amino-2-thioxoethylcarbamate (450 mg, 2.37 mmol), CaO (165 mg, 2.94 mmol), Pd2(dba)3 (365 mg, 0.400 mmol) and dppf (885 mg, 1.60 mmol) in MeCN (7 mL) was added a mixture of 2-chloro-4-iodoaniline (500 mg, 1.97 mmol) in MeCN (3 mL) at 20 C, the resulting mixture was stirred at 60 C under N2 atmosphere for 8 hours. After cooling to room temperature, the mixture was diluted with water (20 mL), extracted with EtOAc (30 mL X 3), washed with brine (10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to give a residue, which was purified by column (eluted: PE/EtOAc=6/1) to afford 500 mg (yield: 87%) of compound T1 as a yellow powder.
With copper(l) iodide; sodium azide; potassium carbonate; N,N`-dimethylethylenediamine In dimethyl sulfoxide at 80℃; for 20h; Sealed tube; regioselective reaction;
General procedure: 2-iodoaniline (54.8 mg, 0.25 mmol) 1a, sodium azide (19.5 mg, 0.3mmol) 3, CuI (4.8 mg, 0.025 mmol), K2CO3 (34.5 mg, 0.25 mmol),phenylacetaldehyde (58 μL, 0.5 mmol) 2a, (DMEDA) (3 μL, 0.025mmol) were taken in a round bottom flask equipped with stirrer in 1.0mL of DMSO. The reaction mixture was heated to 80 °C for 20 h.After cooling the room temperature, to the reaction mixture wasadded water (2 mL), and extracted with EtOAc (310 mL). Thecombined organic phases were washed with brine (25 mL), driedover anhydrous MgSO4 and concentrated in vacuo. The residue wassubjected to flash column chromatography with petroleum/ethylacetate (20/1) to afford the final product 4aa as light yellow solid
With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,2-dimethoxyethane; water; for 16h;Reflux;
4-chloro-2-iodoaniline (90 g, 355 mmol), phenylboronic acid (52.0 g, 426 mmol), potassium carbonate (147 g, 1065 mmol), DME (720 ml) and water (720 ml) were added to a 5 L flask. After degassing, bis(triphenylphosphine)palladium(II) chloride (4.98 g, 7.10 mmol) was added to the mixture and refluxed for 14 hours. After completion, the reaction mixture was diluted with EtOAc (1 L).And separate the two layers. The aqueous layer was extracted with EtOAc (EtOAc m.The resulting oil was purified by column chromatography using EtOAc /hexanes.5-Chloro-[1,1'-biphenyl]-2-amine (90% yield) was obtained.
With azobisisobutyronitrile; tri-n-butyl-tin hydride; In dimethyl sulfoxide; toluene; at 100℃; for 16h;
To a mixture of 4-chloro-2-iodoaniline (0.500 g, 1.97 mmol) in DMSO (10 mL) was added ethyl acrylate (0.643 mL, 5.92 mmol), tributyltinhydride (0.793 mL, 2.96 mmol) and (E)-2,2'-(diazene-1,2-diyl)bis(2-methylpropanenitrile) in toluene (1.97 mL, 0.39 mmol). The resulting mixture was heated at 100C for 16 h. The reaction was diluted with DCM and washed with brine. The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was filtered through a silica plug, using 40% EtOAc in Heptane as the eluent. Fractions containing the desired product was pooled and concentrated under reduced pressure to give compound 21A as a crude solid (0.210 g, 59%). The crude material was used in the next reaction step without further purifications.
With copper(l) chloride; In N,N-dimethyl-formamide; at 110℃; for 6h;Inert atmosphere; Sealed tube;
General procedure: A 25 mL Wattecs reaction tube was charged with 2-haloaniline 1 (0.6 mmol), potassium O-ethyl dithiocarbonate 2 (1.8 mmol),CuCl (0.06 mmol), and DMF (2 mL). The reaction vessel was flushed with argon three times and sealed. Then the mixture was stirred electromagnetically in an oil bath at 110C for 6 h.The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, and then HCl (3 mL, 3 mol/L) was added and stirred for another 30 min. The reaction mixture solution was extracted by ethyl acetate (3 × 20 mL). Subsequently, the combined organic solutions were dried by anhydrous sodium sulfate and the target product was purified by chromatography on a silica gel column (eluent: petroleum ether/ethyl acetate) togive the corresponding pure product 3. Complete characterization characterizationof the products (all known) is found in the Supplemental Materials (Figures S1-S13).
77%
With iron(III) trifluoride; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 110℃; for 18h;Inert atmosphere; Sealed tube;
General procedure: A 25 mL reaction tube was charged with 2-haloaniline 1 (0.6 mmol), potassium o-ethyldithiocarbonate 2 (1.8 mmol), FeF3 (0.06 mmol), 2,2?-bis(diphenylphosphino)-1,1?-binaphthyl (0.03 mmol) and DMF (4 mL). The reaction vessel was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically in an oil bath at 110 for 3 - 21 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, then 4 mL HCl (3mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by ethyl acetate (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous sodium sulfate and the target product was purified by silica gel colum chromatography (eluent: petroleum ether / ethylacetate) to give the corresponding pure product 3.
With sodiumsulfide nonahydrate; In N,N-dimethyl-formamide; at 110℃; for 12h;Sealed tube; Inert atmosphere;
General procedure: A sealed tube (50 mL) was charged with 2-haloaniline 1a (2mmol), CS2 (10 mmol), Na2S (4mmol) and DMF (2 mL) at room temperature under an argon gas atmosphere and the tube was flushed with argon for three times and sealed. Then the mixture was stirred electromagnetically at 110 C for 12 hours. The reaction process was monitored by TLC on silica gel. After the reaction was completed, the reaction mixture was cooled to room temperature, 2 mL HCl (3 mol/L) was added and stirred for 30 minutes. Then the reaction mixture solution was extracted by dichloromethane (3*20 mL). Subsequently, the combined organic solution were dried by anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel colum chromatography (eluent: petroleum ether / ethyl acetate) give the corresponding pure product 2a.
(E)-4-((4-chloro-2-iodophenyl)imino)dihydrofuran-2(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With 1-butyl-3-methylimidazolium hydroxide In water at 20℃; for 8h; Green chemistry;
2,8-Dioxa-cyclopenta[a]inden-3-one (3): Procedure
General procedure: A mixture of 2-iodophenol 1 (2.0 mmol), tetronic acid 2 (2.0 mmol), water 3 ml and [bmIm]OH (10 mol%) was stirred at room temperature for 5 h. After completion of reaction as indicated by TLC, 20 mL of water was added to the reaction mixture and stirred well. The product was extracted with EtOAc (3 * 20 mL). The combined organic layer were dried over anhydrous Na2SO4 to afford the crude product and recrystallized from ethanol to obtain analytically pure compound 4 (75-90%). After isolation of the product, the remaining aqueous layer containing the ionic liquid was washed with ether (2x10 mL) to remove organic impurity and filtered. The filtrate was extracted with dichloro methane (2 * 10 mL), dried over MgSO4 and evaporated under reduced pressure to afford [bmIm]OH, which was reused thrice in subsequent runs without further purification.
General Procedure A: Synthesis of indoles from 2-iodoanilines. To a solution of aniline (1 equiv) in DMF (0.5 M) was added DABCO (3 equiv). After 30 minutes, pyruvic acid (3 equiv) was added over 10 minutes. The reaction flask was purged with argon, then Pd(OAc)2 (5 mol %) was added and the reaction flask was purged with argon again. The reaction was heated to 105 C for 1 hour then cooled to room temperature. After an hour at this temperature the reaction was acidified to a pH of 3 with 1M HC1. The total volume was doubled with water and the mixture was filtered. The brown solid was washed with two portions of water, and the crude acid was carried directly to the next step. The acid was dissolved in EtOH (0.2 M) and SOCl2 (1.8 equiv) was slowly added. The mixture was heated to reflux overnight, and then concentrated to dryness. The solid was dissolved in acetone then dry-loaded onto silica gel and purified by column chromatography, yielding the product as a tan solid.
1-(2-((2-amino-5-chlorophenyl)ethynyl)phenyl)ethanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 20℃; for 5h;Inert atmosphere;
General procedure: To a 50 mL oven-dried flask containing a magnetic stirring bar, Pd(PPh3)2Cl2 (14.0 mg, 0.02 mmol, 1.0 mol %), CuI (2.0 mg, 0.01 mmol, 0.5 mol %), 4-(tert-butyl)-2-iodoaniline (550.0 mg, 2.0 mmol), 2 (317.0 mg,2.2 mmol) [26], and Et3N (10 mL) were added in sequence under argon atmosphere at room temperature. The resulting reaction mixture was stirred for 5 h, then the reaction mixture was filtered through a shortpad of celite, and the solid was washed with EtOAc (20 mL). The combined organic phase was concentrated under reduced pressure, andthe residue was purified by column chromatography on silica gel(eluent: petroleum ether/ethyl acetate=10:1) to afford pure product4c in 75% yield.
A 25 mL two-necked round bottom flask was fitted with condenser. Initially 0.1 g substrate (0.001 mol) was added to the flask followed by 10 mL solvent. After this 0.28 g iodine (0.001 mol) was added to the same flask followed by addition of 0.02 g catalyst. The reaction was carried out at different temperatures (Table 1) for 2-6 hrs. After completion of the reaction, 5 mL water was added to the reaction flask to stop the reaction. The reaction was monitored by GC analysis.
Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed <strong>[1201663-81-1]3-chloro-5-(chlorosulfonyl)-4-hydroxybenzoic acid</strong> (1 g, 3.7 mmol, 1 equiv), 4-chloro-2-iodoaniline (935 mg, 3.7 mmol, 1.00 equiv), pyridine (10 mL). The resulting solution was stirred for 0.5 h at room temperature. The reaction was then quenched by the addition of 100 mL of water/ice. The resulting solution was extracted with 3x100 mL of ethyl acetate. The resulting mixture was washed with 1 xlOO mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated. This resulted in 650 mg of 17.2 as a white solid.
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