* 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] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 24, p. 4385 - 4388
4
[ 22121-86-4 ]
[ 29289-13-2 ]
[ 16382-15-3 ]
Reference：
[1] European Journal of Organic Chemistry, 2011, # 34, p. 6902 - 6908
5
[ 29289-13-2 ]
[ 39576-82-4 ]
Reference：
[1] Synlett, 2006, # 1, p. 65 - 68
6
[ 75-15-0 ]
[ 29289-13-2 ]
[ 2268-79-3 ]
Yield
Reaction Conditions
Operation in experiment
94%
With sodiumsulfide nonahydrate In N,N-dimethyl-formamide at 110℃; for 7 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.
67.1%
With sodium sulphide nonahydrate In N,N-dimethyl-formamide at 110℃; for 12 h; Inert atmosphere
To the reaction tube was added 0.50 mmol (0.1435 g) of 2-iodo-4- (trifluoromethyl) aniline, 0.25 mmol (0.0600 g) of sodium hexahydrate, and then 2 mL of N, N-dimethylformamide and 1.50 mmo 1 (0.1142 g) of carbon disulfide, the reaction was stirred at 110 ° C for 12 hours. After TLC was tested, the reaction was complete. The reaction mixture was extracted with methylene chloride three times. The organic phases were combined and dried over anhydrous magnesium sulfate for 2 hours. The desiccant was removed by filtration and the residue was evaporated under reduced pressure to remove the dichloromethane solvent To obtain a crude product. The crude product was subjected to column chromatography (200-300 mesh silica gel) eluting with petroleum ether and ethyl acetate (8: 1-2: 1) to give purity of more than 99percent Of a white powder of 6-trifluoromethyl-2-mercaptobenzothiazole in a yield of 45.4percent
With iron(III) trifluoride; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In N,N-dimethyl-formamide at 110℃; for 10 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.
44.2%
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).
Reference：
[1] Synthetic Communications, 2015, vol. 45, # 20, p. 2378 - 2385
[2] Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 5, p. 699 - 701
8
[ 29289-13-2 ]
[ 544-92-3 ]
[ 5925-93-9 ]
Reference：
[1] Journal of the American Chemical Society, 2004, vol. 126, # 39, p. 12248 - 12249
9
[ 29289-13-2 ]
[ 5925-93-9 ]
Reference：
[1] Journal of the American Chemical Society, [2] Journal of the American Chemical Society, 2009, vol. 131, p. 7238 - 7239
[3] Advanced Synthesis and Catalysis, 2012, vol. 354, # 16, p. 2899 - 2904
10
[ 29289-13-2 ]
[ 5925-93-9 ]
Reference：
[1] Synlett, 2006, # 1, p. 65 - 68
11
[ 29289-13-2 ]
[ 3337-66-4 ]
Reference：
[1] American Chemical Journal, 1909, vol. 42, p. 457
[2] American Chemical Journal, 1909, vol. 42, p. 457
12
[ 106-49-0 ]
[ 29289-13-2 ]
Yield
Reaction Conditions
Operation in experiment
95%
With iodine; sodium hydrogencarbonate In dichloromethane; water at 20℃;
Step 1: Preparation of 2-iodo-4-methylaniline To a solution of 4-methylaniline (53.5 g, 500 mmol) in DCM (200 mL) was added a solution of NaHCO3 (50.4 g) in water (500 mL), and then I2(127 g) was added. The mixture was stirred at rt overnight. The mixture was treated with aqueous NaHSO3 and extracted with DCM. The combined organic layers were washed with brine, dried over Na2SO4, and then concentrated in vacuo to afford the product as brown oil (110 g, yield 95percent). 1H NMR (300 MHz, CDCl3): δ 7.48 (dd, J=1.8 & 0.6 Hz, 1H), 6.96 (dd, J=8.1 & 1.8 Hz, 1H), 6.67 (d, J=8.1 Hz, 1H), 3.98 (bs, 2H), 2.22 (s, 3H) ppm.
94%
With N-iodo-succinimide; [bis(trifluoromethanesulfonyl)imidate](triphenylphosphine)gold(I) 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.
90%
With 1,4-dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate In neat (no solvent) at 20℃; for 0.166667 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.
84%
With iodine; sodium hydrogencarbonate In dichloromethane; water at 0 - 25℃; for 22 h; Inert atmosphere
A solution of para-toluidine (11; 1.61 g, 15 mmol) and NaHCO3 (3.78 g, 45 mmol) inH20/CH2CI2 1:2 (90 mL) was treated with 12 (3.81 g, 15 mmol) at 0 00 under Ar and stirred at25 00 for 22 h. The layers were separated, and the aqueous layer was extracted with CH2CI2(2x 30 mL). The combined organic layers were washed with brine (lx 40 mL) and evaporated.Flash column chromatography (Si02; hexane/EtOAc 100:0 to 95:5) yielded 2-iodo-4-methylaniline (2.95 g, 84percent) as a brown oil.Rf = 0.22 (Si02; hexane/EtOAc 95:5, UV 254 nm); 1 H NMR (400 MHz, CDCI3): d 7.47 (dd, J =1.4,0.7 Hz, 1 H; H—C(3)), 6.95 (dd, J = 8.1, 1.9 Hz, 1 H; H—C(S)), 6.68 (d, J = 8.1 Hz, 1 H; H—C(6)),4.05—2.57 (br. s, 2 H; NH2), 2.20 ppm (s, 3 H; Me).
75%
With iodine; sodium hydrogencarbonate In water at 0 - 20℃; for 12 h;
This was prepared following a modified literature reported procedure.29 Thus, p-toluidine (6, 2g, 18.7mmol), 96 NaHCO3 (2.35g, 28mmol) and 97 water (20ml) were introduced in a100ml round bottom flask. The reaction mixture was allowed to cool to 0°C with stirring and 98 iodine (0.96g) was added in portion at an interval of 15min. After completion of the addition of iodine the reaction mixture was allowed to stir at room temperature for 12h. Completion of the reaction was monitored by TLC. The reaction mixture was extracted with ethyl acetate and the organic fractions were washed with Na2S2O3. The organic fractions were collected and evaporated to dryness to get the crude reaction mixture which was purified by silica gel (60-120 mesh) column chromatography using 15:1 Hex:EtOAc as eluent affording the 15 product 7 as blackish brown solid. Yield=75percent (3.21g). 1H NMR (600MHz, CDCl3) δ 7.48 (s, 1H), 6.95 (d, J=7.7Hz, 1H), 6.66 (d, J=8.1Hz, 1H), 3.95 (s, 2H), 2.21 (s, 3H); 13C NMR (150MHz, CDCl3) δ 144.4, 139.1, 130.1, 129.6, 114.7, 84.4, 77.1, 19.9.
57%
With calcium carbonate In methanol; chloroform at 20℃; for 3 h;
2-Iodo-4-Methylaniline (21) To a stirred solution of p-toluidine (14.10 g, 132 mmol) in 5:1 CHCl3/MeOH (1000 mL) were added CaCO3 (19.8 g, 197 mmol) and BTEA.Cl2 (59.06 g, 151 mmol) at room temperature. After stirring for 3 h, the reaction mixture was washed thrice with a solution of NaHSO3 (5percent w/v) and once with water. The organic layer was dried over MgSO4 and subsequently filtered. The filtrate was concentrated under reduced pressure to give 27 as a yellow powder (17.42 g, 57percent): 1H NMR (300 MHz, CDCl3) δ 7.47 (d, J=1.2 Hz, 1H), 6.95 (dd, J=8.1, 1.2 Hz, 1H), 6.66 (d, J=8.1 Hz, 1H), 3.95 (s, 2H), 2.21 (s, 3H).
Reference：
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[2] Advanced Synthesis and Catalysis, 2017, vol. 359, # 15, p. 2640 - 2652
[3] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 8, p. 897 - 904
[4] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 19, p. 2805 - 2810
[5] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 5, p. 1031 - 1038
[6] RSC Advances, 2014, vol. 4, # 12, p. 6267 - 6274
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[8] Patent: US2013/131016, 2013, A1, . Location in patent: Paragraph 0361; 0362; 0388; 0389
[9] Organic Preparations and Procedures International, 2002, vol. 34, # 6, p. 647 - 651
[10] Synlett, 2014, vol. 25, # 3, p. 399 - 402
[11] Bulletin of the Chemical Society of Ethiopia, 2015, vol. 29, # 1, p. 157 - 162
[12] Organic and Biomolecular Chemistry, 2014, vol. 12, # 16, p. 2514 - 2518
[13] Bulletin of the Korean Chemical Society, 2012, vol. 33, # 8, p. 2619 - 2622
[14] Synthetic Communications, 2013, vol. 43, # 21, p. 2913 - 2925
[15] Patent: WO2016/44313, 2016, A1, . Location in patent: Page/Page column 52
[16] Organic and Biomolecular Chemistry, 2017, vol. 15, # 10, p. 2246 - 2252
[17] Organic Letters, 2013, vol. 15, # 4, p. 848 - 851
[18] Organic Letters, 2011, vol. 13, # 12, p. 3242 - 3245
[19] Organometallics, 2016, vol. 35, # 4, p. 595 - 604
[20] Organic Letters, 2017, vol. 19, # 13, p. 3402 - 3405
[21] Chemistry - A European Journal, 2010, vol. 16, # 10, p. 3005 - 3008
[22] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 2, p. 600 - 602
[23] Organic and Biomolecular Chemistry, 2016, vol. 14, # 6, p. 2127 - 2133
[24] Tetrahedron, 2018, vol. 74, # 18, p. 2218 - 2229
[25] Journal of Organic Chemistry, 1999, vol. 64, # 26, p. 9646 - 9652
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[28] Helvetica Chimica Acta, 2010, vol. 93, # 2, p. 345 - 349
[29] Patent: US2014/31559, 2014, A1, . Location in patent: Paragraph 0270
[30] Advanced Synthesis and Catalysis, 2012, vol. 354, # 16, p. 2899 - 2904
[31] Synthetic Communications, 1992, vol. 22, # 22, p. 3215 - 3219
[32] Organic Preparations and Procedures International, 2007, vol. 39, # 1, p. 90 - 93
[33] Chemical Communications, 2017, vol. 53, # 24, p. 3481 - 3484
[34] Journal of Organic Chemistry, 2002, vol. 67, # 3, p. 932 - 934
[35] Organic Letters, 2013, vol. 15, # 11, p. 2616 - 2619
[36] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical, 1980, vol. 19, # 12, p. 1179 - 1182
[37] American Chemical Journal, 1909, vol. 42, p. 457
[38] Journal of the Chemical Society, 1953, p. 3711
[39] Journal fuer Praktische Chemie (Leipzig), 1919, vol. <2>99, p. 270
[40] Tetrahedron Letters, 1989, vol. 30, # 8, p. 899 - 902
[41] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 24, p. 4385 - 4388
[42] Journal of Organic Chemistry, 2006, vol. 71, # 18, p. 7079 - 7082
[43] Journal of Organic Chemistry, 2001, vol. 66, # 13, p. 4525 - 4542
[44] Journal of Organic Chemistry, 2002, vol. 67, # 18, p. 6395 - 6405
[45] Journal of Organic Chemistry, 2007, vol. 72, # 15, p. 5731 - 5736
[46] Angewandte Chemie - International Edition, 2007, vol. 46, # 12, p. 2074 - 2077
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[48] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 5, p. 1351 - 1357
[49] Synthesis (Germany), 2016, vol. 48, # 6, p. 855 - 864
[50] Journal of Organic Chemistry, 2016, vol. 81, # 22, p. 10987 - 10999
13
[ 496-72-0 ]
[ 29289-13-2 ]
Yield
Reaction Conditions
Operation in experiment
67%
Stage #1: With water; sodium nitrite In neat (no solvent) at 20℃; Stage #2: With potassium iodide In neat (no solvent) at 20℃;
General procedure: An aromaticamine (1 mmol), nanomagnetic-supported sulfonic acid (c-Fe2O3–SO3H)(0.65 g), NaNO2 (2 mmol, 0.138 g), and 0.2 mL of H2O were homogenized bygrinding in a mortar with a pestle for a few minutes. Formation of a reddishbrowngas was observed as soon as H2O was added. The diazotization reactionlasted for approximately 5–30 min. Next, KI (2.5 mmol, 0.415 g) was added tothe diazonium salt and grinding was continued for 10–20 min. After completionof the reaction, the mixture was triturated with EtOAc (5 mL). The c-Fe2O3–SO3K was separated from the solution using a magnetic bar. The organic layerwas treated with aq 10percent Na2SO3 (15 mL), then dried over anhydrous Na2SO4.After evaporation of the solvent, the crude product was afforded. Purifiedproducts were obtained by recrystallization from ethanol or by flashchromatography (n-hexane–EtOAc, 95:5).
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
16
[ 104-94-9 ]
[ 29289-13-2 ]
Reference：
[1] Synlett, 2006, # 1, p. 65 - 68
17
[ 784183-53-5 ]
[ 29289-13-2 ]
Reference：
[1] Synlett, 2006, # 1, p. 65 - 68
18
[ 52488-29-6 ]
[ 29289-13-2 ]
Reference：
[1] Journal of the American Chemical Society, 2015, vol. 137, # 30, p. 9531 - 9534
19
[ 100377-05-7 ]
[ 106-49-0 ]
[ 29289-13-2 ]
Reference：
[1] Zhurnal Obshchei Khimii, 1956, vol. 26, p. 3139,3143; engl. Ausg. S. 3499, 3503
20
[ 106-49-0 ]
[ 620-93-9 ]
[ 29289-13-2 ]
[ 501-60-0 ]
Reference：
[1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1984, vol. 23, # 7, p. 678 - 679
General procedure: The appropriate o-(o-aminophenylethynyl) trifluoroacetanilides 5 and o-(oaminophenylethynyl)anilines 15 were prepared, usually in high yields, via a Sonogashiracross-coupling of 2-iodotrifluoroacetanilides or 2-iodoaniline with 2-ethynylanilines.
With ammonium peroxydisulfate; potassium iodide In methanol; water at 20℃;
1: 13%
2: 40%
With potassium dichloroiodate monohydrate In dichloromethane at 25℃; for 1h;
Iodination of Thiophenes and Benzene Derivatives with KICl2*H2O; General Procedure
General procedure: The conditions for the iodination of thiophene derivatives were optimized by repeating the reaction for different times, substrates and reagent ratios, and temperatures (Table 1). The progress of the reaction was monitored by TLC. The substrate (1 mmol) was dissolved or suspended in the solvent (5 mL). Next, KICl2*H2O (510 mg, 2 mmol) was added to the mixture. The mixture was stirred for the time and at the temperature specified in Tables 1-5. The r.t. reactions were carried out in a glass vial, and the elevated temperature reactions were carried out in a pressure tube sealed with a screw cap, in an oil bath. The progress of the reaction was monitored by TLC. An aliquot of aq Na2S2O3 (5 mL, 5% v/v) was added to quench the reaction. The mixture was then washed with H2O (3 5 mL) in a separatory funnel. The reaction mixtures carried out in H2O first were extracted with CH2Cl2 (3 5 mL) and then washed with H2O (3 5 mL). The combined organic layers were dried (MgSO4) and filtered through Whatman filter paper (diameter 9 cm, pore size 11 m). The iodinated product was obtained by evaporation of the filtrate. The purified product was obtained by column chromatography or recrystallization. For p-hydroxybenzaldehyde, 0.5 mmol of the substrate was dissolved in H2O (5 mL), and then KICl2*H2O (510 mg, 2 mmol) was added to the mixture. Next, the mixture was allowed to stir for 10 min at 50 °C. The precipitate was filtered through Whatman filter paper (diameter 9 cm, pore size 11 m) and purified by recrystallization from CH2Cl2. The solid-state reactions were performed by mixing of the substrate and reagent in a mortar and grinding with a pestle for the time specified in Tables 5 and 6, to obtain a homogeneous mixture. The aqueous solution of Na2S2O3 (5 mL, 5% v/v) was used to quench the reaction. The product was collected by filtration through Whatman filter paper (diameter 9 cm, pore size 11 m).
With hydrogenchloride; potassium iodate; potassium iodide In methanol; water at 20℃; for 3h;
Synthesis of substituted 2-iodoaniline 24-27
A solution of substituted aniline 22,23 (10 g; 93.30 mmol), potassium iodide (10.37g; 62.52 mmol) and potassium iodate (6.59 g; 30.79 mmol) was prepared in methanol (50mL) and water (200 mL). The aqueous solution of hydrochloric acid (10 mL, 95.71mmol) was added drop wise to the mixture for 40 to 45 minutes. The reaction mixturewas diluted with water (500 mL) after 3 hours and extracted with dichloromethane (3×50mL). The combined organic extract was washed with dilute sodium thiosulphate (5%),water, brine water, dried over anhydrous sodium sulfate and concentrated under reducedpressure. The crude product was purified by column chromatography on silica gel usingn-hexane /ethyl acetate (4:1) as eluant and 2-iodoanilines 24,25 and 2,6-diiodoanilines26,27 were isolated in good yield.
With sodiumsulfide nonahydrate; In N,N-dimethyl-formamide; at 110℃; for 7h;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.
67.1%
With sodium sulphide nonahydrate; In N,N-dimethyl-formamide; at 110℃; for 12h;Inert atmosphere;
To the reaction tube was added 0.50 mmol (0.1435 g) of 2-iodo-4- (trifluoromethyl) aniline, 0.25 mmol (0.0600 g) of sodium hexahydrate, and then 2 mL of N, N-dimethylformamide and 1.50 mmo 1 (0.1142 g) of carbon disulfide, the reaction was stirred at 110 C for 12 hours. After TLC was tested, the reaction was complete. The reaction mixture was extracted with methylene chloride three times. The organic phases were combined and dried over anhydrous magnesium sulfate for 2 hours. The desiccant was removed by filtration and the residue was evaporated under reduced pressure to remove the dichloromethane solvent To obtain a crude product. The crude product was subjected to column chromatography (200-300 mesh silica gel) eluting with petroleum ether and ethyl acetate (8: 1-2: 1) to give purity of more than 99% Of a white powder of 6-trifluoromethyl-2-mercaptobenzothiazole in a yield of 45.4%
4-Methyl-morpholine (1.60 g, 15.9 mmol) was added to a suspension of fumaric acid monoethyl ester (2.30 g, 15.9 mmol) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (4.40 g, 15.9 mmol) in THF (50 mL) and the suspension was stirred at room temperature for 20 min. A solution of 2-iodo-p-toluidine (3.35 g, 14.4 mmol) in THF (5 mL) was added and the suspension was stirred overnight. The reaction mixture was diluted with water, extracted with diethyl ether washed with saturated NaHCO3, water, 2% hydrochloric acid, brine, dried (NaSO4), and evaporated. The residue was added to a mixture of sodium hydride (0.371 g, 15.4 mmol) in THF (25 mL), which was cooled to 0 C. The solution was stirred for 30 min at 0 C and at room temperature for another 30 min. Methyl iodide (2.74 g, 19.3 mmol) was added and the reaction was stirred for 2 h. The solvent was evaporated and the residue dissolved in ethyl acetate, washed with water, dried (MgSO4) and evaporated. The resulting crude was recrystallized from diethyl ether to give the title compound (3.65 g, 68%) as an off-white solid.
With copper(I) oxide; caesium carbonate; N,N`-dimethylethylenediamine In N,N-dimethyl-formamide at 140℃; for 16h; Inert atmosphere;
General experimental procedure
General procedure: A flask was charged with Cu2O (14 mg, 0.1 mmol), Cs2CO3 (977 mg, 3 mmol), o-haloaniline (1 mmol) and amidine hydrochloride (1.5 mmol) in 2 mL DMF under nitrogen atmosphere. The mixture was stirred at room temperature and DMEDA (20 mL, 0.2 mmol) was added via syringe. The reaction mixture was then stirred in a preheated oil bath at 140 C for 16 h, and then cooled to room temperature. The inorganic salt was filtered off and ethyl acetate, water was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4, and concentrated in vacuum.The residue was purified by column chromatography on silica gelusing petroleum ether/ethyl acetate as eluent to provide the desired product.
With copper(I) oxide; caesium carbonate; N,N`-dimethylethylenediamine; In N,N-dimethyl-formamide; at 140℃; for 16h;Inert atmosphere;
General procedure: A flask was charged with Cu2O (14 mg, 0.1 mmol), Cs2CO3 (977 mg, 3 mmol), o-haloaniline (1 mmol) and amidine hydrochloride (1.5 mmol) in 2 mL DMF under nitrogen atmosphere. The mixture was stirred at room temperature and DMEDA (20 mL, 0.2 mmol) was added via syringe. The reaction mixture was then stirred in a preheated oil bath at 140 C for 16 h, and then cooled to room temperature. The inorganic salt was filtered off and ethyl acetate, water was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4, and concentrated in vacuum.The residue was purified by column chromatography on silica gelusing petroleum ether/ethyl acetate as eluent to provide the desired product.
2. Experimental methods
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.
With potassium tert-butylate; In N,N-dimethyl-formamide; at -60 - -30℃; for 1.5h;
General procedure: To a cooled solution of KOt-Bu (3,7 g, 30 mmol) in DMF (50 mL) was added dropwise at -60 C a solution of the appropriate 2-iodoaniline (9.6 mmol) in DMF (3 mL) and the nitroarene (9.6mmol) in DMF (8 mL). The mixture was stirred at -60 C for 0.5h then the temperature was raised slowly to -30 C, and the reaction was continued for an additional 1 h, poured into sat.NH4Cl solution (200 mL) and extracted with EtOAc. The extract was washed with H2O, brine, and dried with Na2SO4. After evaporation,the crude product mixture was subjected to column chromatography (SiO2, hexane-toluene). For analytical data, seethe Supporting Information.
With iron(III) trifluoride; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In N,N-dimethyl-formamide; at 110℃; for 10h;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.
44.2%
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).
In a 20 mL dehydrated deoxygenated Schlenk tube, <strong>[4545-21-5]acetophenone p-toluenesulfonylhydrazone</strong>(0.30 mmol, 86.4 mg), 2-iodo-4-methylaniline (0.2 mmol, 46.6 mg), bistriphenylphosphine palladium dichloride (0.02 mmol,14.0 mg), sodium tert-butoxide (1.2 mmol, 115.2 mg) 3.0 mL diethylene glycol dimethyl ether (diglyme), and finally to the reaction tube Inject 0.1MPa of CO2. The sealed reaction tube was heated and stirred in an oil bath at 140 C for about 24 hours. use1.5 mL of 1 M hydrochloric acid solution for acidification of the reaction solution, and then ethyl acetate (4mL × 5) extraction, combined organic The final product was purified by column chromatography and then dried to give 30.5 mg of a white solid powder solid in 65% yield.
1-(2-((2-amino-5-methylphenyl)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.
2-(4-methylphenyl)-6-methyl-4H-3,1-benzoxazin-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With N-ethyl-N,N-diisopropylamine In toluene at 110℃; for 24h; Inert atmosphere;
Heterogeneous Palladium-Catalyzed Carbonylative Synthesis of 2-Arylbenzoxazinones 3; General Procedure
General procedure: MCM-41-Pd(OAc)2 (5 mol%), 2-iodoaniline 1 (1.2 mmol) and aryl iodide2 (1.0 mmol) (if solid). The vial was purged with argon and then aryl iodide 2 (1.0 mmol) (if liquid), DiPEA (4.0 mmol), and toluene (2mL) were injected by syringe. The vial was placed in an alloy plate and the plate was then transferred into a 300 mL autoclave under argon. After the autoclave had been flushed with CO (3×), the CO pressure was adjusted to 5 bar and the reaction was carried out for 24 h at 110°C. Upon completion of the reaction, the autoclave was cooled to ambient temperature and the pressure was released cautiously. EtOAc(10 mL) was then added and the resulting mixture was filtered. The Pd catalyst was recovered, by washing with distilled water (2 × 5 mL) and acetone (2 × 5 mL), followed by drying under vacuum at 80 °C for 2 h, and reused in the next cycle. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, light PE-EtOAc, 10:1) to afford the desired product 3.
methyl 4-(6-methyl-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With N-ethyl-N,N-diisopropylamine In toluene at 110℃; for 24h; Inert atmosphere;
Heterogeneous Palladium-Catalyzed Carbonylative Synthesis of 2-Arylbenzoxazinones 3; General Procedure
General procedure: MCM-41-Pd(OAc)2 (5 mol%), 2-iodoaniline 1 (1.2 mmol) and aryl iodide2 (1.0 mmol) (if solid). The vial was purged with argon and then aryl iodide 2 (1.0 mmol) (if liquid), DiPEA (4.0 mmol), and toluene (2mL) were injected by syringe. The vial was placed in an alloy plate and the plate was then transferred into a 300 mL autoclave under argon. After the autoclave had been flushed with CO (3×), the CO pressure was adjusted to 5 bar and the reaction was carried out for 24 h at 110°C. Upon completion of the reaction, the autoclave was cooled to ambient temperature and the pressure was released cautiously. EtOAc(10 mL) was then added and the resulting mixture was filtered. The Pd catalyst was recovered, by washing with distilled water (2 × 5 mL) and acetone (2 × 5 mL), followed by drying under vacuum at 80 °C for 2 h, and reused in the next cycle. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, light PE-EtOAc, 10:1) to afford the desired product 3.
6-methyl-2-(3-thienyl)-4H-benzo[d][1,3]oxazin-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With N-ethyl-N,N-diisopropylamine In toluene at 110℃; for 24h; Inert atmosphere;
Heterogeneous Palladium-Catalyzed Carbonylative Synthesis of 2-Arylbenzoxazinones 3; General Procedure
General procedure: MCM-41-Pd(OAc)2 (5 mol%), 2-iodoaniline 1 (1.2 mmol) and aryl iodide2 (1.0 mmol) (if solid). The vial was purged with argon and then aryl iodide 2 (1.0 mmol) (if liquid), DiPEA (4.0 mmol), and toluene (2mL) were injected by syringe. The vial was placed in an alloy plate and the plate was then transferred into a 300 mL autoclave under argon. After the autoclave had been flushed with CO (3×), the CO pressure was adjusted to 5 bar and the reaction was carried out for 24 h at 110°C. Upon completion of the reaction, the autoclave was cooled to ambient temperature and the pressure was released cautiously. EtOAc(10 mL) was then added and the resulting mixture was filtered. The Pd catalyst was recovered, by washing with distilled water (2 × 5 mL) and acetone (2 × 5 mL), followed by drying under vacuum at 80 °C for 2 h, and reused in the next cycle. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, light PE-EtOAc, 10:1) to afford the desired product 3.
With N-ethyl-N,N-diisopropylamine In toluene at 100℃; for 24h; Inert atmosphere; Autoclave;
General procedure for the carbonylative synthesis of 2-alkylbenzoxazinones underthe catalysis of heterogeneous palladium
General procedure: A 12mL vial equipped with a septum, a small cannula, and a magnetic stirring bar wascharged with 2 P-MCM-41-PdCl2 (0.02 mmol) and 2-iodoaniline (1 mmol). After thevial was purged with argon, acid anhydride (1.5 mmol), DiPEA (2.2 mmol), and drytoluene (2 mL) were injected into the vial by syringe. Then the vial was placed in analloy plate, which was transferred into an autoclave (300 mL) under Ar. After the autoclavebeing flushed with carbon monoxide three times, the pressure of carbon monoxidewas adjusted to 2 bar, and the reaction mixture was stirred at 100 C for 24 h. After theautoclave being cooled to ambient temperature, the CO pressure was cautiouslyreleased. The reaction mixture was diluted with EtOAc (10 mL) and filtered. The catalystwas washed with deionized water (24 mL) and acetone (24 mL), dried at 80 Cin vacuo for 2 h, and reused directly in the next run. The filtrate was washed with water(26 mL), dried over Na2SO4, and evaporated in vacuo. The crude product was purifiedby silica gel column chromatography (light petroleum-ethyl acetate 7:3) todeliver the desired products 3.
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