2-BROMOTHIOPHENE-3-CARBALDEHYDE

In a 250 ml two-necked flask, 11.9 g of 2-bromo-3- (bromomethyl) thiophene (256 g mol- 1, 11.9 g, 46 mmol)Pump without water treatment.Under N2 protection, 20.8 g of IBX (280 g mol-1, 20.8 g, 74 mmol, 1.6 equiv)Add 130ml anhydrous DMSO, 60-70°C oil bath for 3-4 hours.After treatment: add 20ml of deionized water to quench the reaction. The mixture was extracted with dichloromethane, washed with a large amount of methylene chloride, and precipitated as a white solid. The filtrate was collected by suction filtration, dried and concentrated by column chromatography.Eluent petroleum ether / ethyl acetate 40: 1 (V: V).To a solution of (2-bromothiophen-3-yl)methanol (5 g, 26.3 mmol) in THF (60 mL) at 0 °C was added Dess-Martin periodinane (13.4 g, 31.6 mmol) in portions. After stirring at 0 °C for 3 h, water and NaIn a 250 ml two-necked flask, 11.9 g of 2-bromo-3- (bromomethyl) thiophene (256 g mol- 1, 11.9 g, 46 mmol)Pump without water treatment.Under N2 protection, 20.8 g of IBX (280 g mol-1, 20.8 g, 74 mmol, 1.6 equiv)Add 130ml anhydrous DMSO, 60-70°C oil bath for 3-4 hours.After treatment: add 20ml of deionized water to quench the reaction. The mixture was extracted with dichloromethane, washed with a large amount of methylene chloride, and precipitated as a white solid. The filtrate was collected by suction filtration, dried and concentrated by column chromatography.Eluent petroleum ether / ethyl acetate 40: 1 (V: V).To a solution of (2-bromothiophen-3-yl)methanol (5 g, 26.3 mmol) in THF (60 mL) at 0 °C was added Dess-Martin periodinane (13.4 g, 31.6 mmol) in portions. After stirring at 0 °C for 3 h, water and Na2-Bromo-3-thiophenecarboxaldehyde (1.91 g, 10 mmol) was added to a solution of 3-thiopheneacetic acid (1.42 g, 10 mmol), Pd(OAc)2 (224 mg, 0.1 mmol), PPh3 (524 mg, 0.2 mmol), and K2CO3 (2.76 g, 20 mmol) in anhyd DMF (50 mL) and the mixture was stirred to 110 °C for 24 h. The reaction suspension was then cooled to 50 °C and then 2-octyldodecyl bromide (3.61 g, 10 mmol) was added in one portion together with a catalytic amount of Bu4NI (184 mg, 0.5 mmol). The mixture was stirred for a further 24 h. After removal of solvent under reduced pressure, the crude mixture was purified by flash chromatography (SiO2; n-hexanes/EtOAc/CH2Cl2 (10:0.5:0.5). The pure product 6 was obtained as a colorless oil (61percent), together with a small amount of 2-octyldodecyl-3-thiophene acetate (11percent).6 Yield: 3.14 g (61percent); Rf = 0.34 (99:0.5:0.5 hexanes/EtOAc/CH2Cl2). 1H NMR (CDCl3, 300 MHz): delta = 8.56 (s, 1H), 8.36 (d, J = 5.6 Hz, 1H), 7.53 (d, J = 5.6 Hz, 1H), 7.50 (d, J = 5.4 Hz, 1H), 7.44 (d, J = 5.4 Hz, 1H), 4.36 (d, J = 5.7 Hz, 2 H), 1.88 (m, 1H), 1.55-1.20 (m, 34 H), 0.87 (t, J = 7.0 Hz, 6 H). 13C NMR (CDCl3, 75 MHz): delta = 166.9, 137.8, 136.0, 135.6, 134.7, 125.7, 125.4, 125.2, 125.0, 124.2, 122.3, 67.8, 37.4, 31.8, 31.4, 29.9, 29.6, 29.5, 29.4, 29.2, 26.7, 22.6, 14.0. FIA-MS: m/z = 515 [M + 1]+, 1029 [2 M + 1]+. Anal. Calcd for C31H46O2S2: C, 72.32; H, 9.01. Found: C, 72.0; H, 8.8.General procedure: In a 10 mL round bottom flask containing 2 mL of (1 : 4) THF-H2O, Pd(OAc)2 (0.02 mmol), 3-(diphenylphosphino)benzoic acid (L 4 ), (0.04 mmol), CuI (0.05 mmol), 2-bromo benzaldehyde (1 mmol), phenylacetylene (1.2 mmol). K2CO3 (2 mmol), were added and the reaction mixture was stirred at 50 °C for 2 h until the completion of the starting materials as monitored by TLC. Then NH4OAc (1.5 mmol) was added and again the whole reaction mixture was stirred at same temperature for additional 2 hours. After the formation of desired product 4a as confirmed by TLC, the reaction mixture was extracted with ethyl acetate (10 mL) and water (10 mL) and the organic layer was washed with aqueous saturated brine solution and dried over Na2SO4. The solvent was removed under vacuum, and the residue was purified by flash column chromatography on silica gel using ethyl acetate/ hexanes as the eluent to afford the desired product 4a.General procedure: In a 10 mL round bottom flask containing 2 mL of (1 : 4) THF-H2O, Pd(OAc)2 (0.02 mmol), 3-(diphenylphosphino)benzoic acid (L 4 ), (0.04 mmol), CuI (0.05 mmol), 2-bromo benzaldehyde (1 mmol), phenylacetylene (1.2 mmol). K2CO3 (2 mmol), were added and the reaction mixture was stirred at 50 °C for 2 h until the completion of the starting materials as monitored by TLC. Then NH4OAc (1.5 mmol) was added and again the whole reaction mixture was stirred at same temperature for additional 2 hours. After the formation of desired product 4a as confirmed by TLC, the reaction mixture was extracted with ethyl acetate (10 mL) and water (10 mL) and the organic layer was washed with aqueous saturated brine solution and dried over Na2SO4. The solvent was removed under vacuum, and the residue was purified by flash column chromatography on silica gel using ethyl acetate/ hexanes as the eluent to afford the desired product 4a.General procedure: In a 10 mL round bottom flask containing 2 mL of (1 : 4) THF-H2O, Pd(OAc)2 (0.02 mmol), 3-(diphenylphosphino)benzoic acid (L 4 ), (0.04 mmol), CuI (0.05 mmol), 2-bromo benzaldehyde (1 mmol), phenylacetylene (1.2 mmol). K2CO3 (2 mmol), were added and the reaction mixture was stirred at 50 °C for 2 h until the completion of the starting materials as monitored by TLC. Then NH4OAc (1.5 mmol) was added and again the whole reaction mixture was stirred at same temperature for additional 2 hours. After the formation of desired product 4a as confirmed by TLC, the reaction mixture was extracted with ethyl acetate (10 mL) and water (10 mL) and the organic layer was washed with aqueous saturated brine solution and dried over Na2SO4. The solvent was removed under vacuum, and the residue was purified by flash column chromatography on silica gel using ethyl acetate/ hexanes as the eluent to afford the desired product 4a.

Molecular Weight:191.05
XLogP3:2.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:189.90880
Monoisotopic Mass:189.90880
Topological Polar Surface Area:45.3
Heavy Atom Count:8
Complexity:96.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes