2-IODOBENZOTHIAZOLE

To a solution of 2-aminobenzothiazole (6) (3.75g, 25mol) and p-TsOH (15g, 75mmol) in acetonitrile (100ml) was added a mixture solution of KI (10.5g, 65mmol) and NaNOBenzothiazole (1 mmol, 135.9 mg), Perfluoroiodobutane (1.1 mmol, 380.5 mg) was placed in a 10 mL round bottom flask.Add 5 mL of N, N-dimethylformamide and sodium tert-butoxide (0.5 mmol, 48.1 mg).Stir at room temperature for 20 minutes, TLC monitored the endpoint of the reaction.Pour the mixture into waterExtract with dichloromethane, The organic phase is collected, dried, and the dichloromethane is removed by rotary evaporation.Crude product.The crude product was subjected to silica gel column chromatography with petroleum ether and ethyl acetate as eluent (volume ratio = 30:1).2-Iodobenzothiazole (white solid, 257.6 mg, yield 99percent) was obtained.It can also be purified by recrystallization: The crude product is washed with cold water, filtered, and the product is dissolved in ethanol (2 mL).Heat to completely dissolve.Let stand, cool slowly and crystals precipitate.General procedure: To a stirred, cooled (0 °C) solution of 2, 2, 6, 6-tetramethylpiperidine (0.25 mL, 1.5 mmol) in THF (2–3 mL) were successively added BuLi (about 1.6 M hexanes solution, 1.5 mmol) and, 5 min later, ZnClGeneral procedure: To a flame-dried reaction tube was added 1, 3-azoles (0.5 mmol, 1.0 eq), 1, 10-phenoline (0.5 mmol, 1.0 eq), LiOtBu (1.0 mmol, 2.0 eq), CuBrTo a solution of 2-aminobenzothiazole (6) (3.75g, 25mol) and p-TsOH (15g, 75mmol) in acetonitrile (100ml) was added a mixture solution of KI (10.5g, 65mmol) and NaNO2 (3.5g, 50mol) in water (15ml) at 0C. The reaction solution was stirred at 0C for 2h, and then at RTovernight. To the reaction solution was added around 350ml of water, adjust the solution pH to 8-9 with NaHCO3 and added Na2S2O3, filtered and the solid was washed to give brown solid 5.52g (yield 84.7%). TLC: Rf: 0.6 (hexane/ethyl acetate=6/1). MS (ESI) m/z 262 (M++H);1HNMR (CDCl3, 300MHz) delta 8.06 (1H, dd, J1=7.5Hz, J2=1.8Hz), 7.87 (1H, dd, J1=6.9Hz, J2=1.5Hz), 7.50~7.38 (2H, m).General procedure: 2-halobenzo[7]thiazole (0.23 mmol), PdiPPhsL (26.98 mg, 0.023 mmol), Cul (6.6 mg, 0.035 mmo) were placed in a 20 mL oven-dried scintillation vial. The vile was evacuated and flushed three times with argon. Then ethynyltriisopropylsilane (0.15 mL, 0.70 mmol), anhydrous Et3N (1 mL), DMF (1 mL) were added via syringe. The vial was sealed and stirred at 50 C for 16 h. Upon completion, the reaction was quenched with brine, extracted two times with Et20 and concentrated under vacuum. The crude product was purified via flash column chromatography to offer the desired product.2-((Triisopropylsilyl)ethynyl)benzo[d]thiazole (125a). Colorless liquid (hexanes :ethyl acetate = 40:1, 87% yield). ^-NMR (CDCh, 300 MHz) d 8.05 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.54 - 7.47 (m, 1H), 7.46 - 7.40 (m, 1H), 1.16 (s, 18H). 13C-NMR (CDCh, 75 MHz) d 152.98, 148.69, 135.47, 126.90, 126.52, 123.96, 121.48, 101.02, 98.98, 18.83, 11.39.Benzothiazole (1 mmol, 135.9 mg), Perfluoroiodobutane (1.1 mmol, 380.5 mg) was placed in a 10 mL round bottom flask.Add 5 mL of N, N-dimethylformamide and sodium tert-butoxide (0.5 mmol, 48.1 mg).Stir at room temperature for 20 minutes, TLC monitored the endpoint of the reaction.Pour the mixture into waterExtract with dichloromethane, The organic phase is collected, dried, and the dichloromethane is removed by rotary evaporation.Crude product.The crude product was subjected to silica gel column chromatography with petroleum ether and ethyl acetate as eluent (volume ratio = 30:1).2-Iodobenzothiazole (white solid, 257.6 mg, yield 99%) was obtained.It can also be purified by recrystallization: The crude product is washed with cold water, filtered, and the product is dissolved in ethanol (2 mL).Heat to completely dissolve.Let stand, cool slowly and crystals precipitate.General procedure: To a stirred, cooled (0 C) solution of 2, 2, 6, 6-tetramethylpiperidine (0.25 mL, 1.5 mmol) in THF (2-3 mL) were successively added BuLi (about 1.6 M hexanes solution, 1.5 mmol) and, 5 min later, ZnCl2'TMEDA14 (0.13 g, 0.50 mmol). The mixture was stirred for 15 min at 0 C before introduction of the substrate (1.0 mmol) at 0-10 C. After 2 h at room temperature, a solution of I2 (0.38 g, 1.5 mmol) in THF (4 mL) was added. The mixture was stirred overnight before addition of an aqueous saturated solution of Na2S2O3(4 mL) and extraction with AcOEt (3 20 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. To the crude iodide were added Cs2CO3(0.65 g, 2.0 mmol), Cu powder (13 mg, 0.20 mmol), the azole (1.5 mmol) and MeCN (5 mL) and the resulting mixture was heated under reflux for 24 h. Filtration over Celite, washing with AcOEt, removal of the solvent and purification by chromatography on silica gel (the eluent is given in the product description) led to the compound described below.General procedure: To a flame-dried reaction tube was added 1, 3-azoles (0.5 mmol, 1.0 eq), 1, 10-phenoline (0.5 mmol, 1.0 eq), LiOtBu (1.0 mmol, 2.0 eq), CuBr2 (0.10 mmol, 0.2 eq) and iodine (0.75 mmol, 1.5 eq). Dry 1, 4-dioxane (2 mL) was added to the mixture and the mixture was heated to 80C by putting the reaction tube to a preheated oil bath until the products were not increased. The mixture was cooled to room temperature and filtered through a short pad of silica gel. The silica gel was washed with EtOAc (20 mL) and the combined the organic phase was concentrated under reduced pressure to give a residue which was purified by silica gel column chromatography to afford the iodination product.

Molecular Weight:261.08
XLogP3:3.3
Hydrogen Bond Acceptor Count:2
Exact Mass:260.91092
Monoisotopic Mass:260.91092
Topological Polar Surface Area:41.1
Heavy Atom Count:10
Complexity:131
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes