7-BROMO-BENZO[B]THIOPHENE

Preparation of 7-Bromobenzo(b)thiophene Preparation of 7-Bromobenzo(b)thiophene SchemeI, To a gently refluxing mixture of PPA(22.2 g) and PhCl (75 mL), was added a solution of (2‑bromophenyl)(2, 2-diethoxyethyl)sulfane(10.00 g, 32.76 mmol) in PhCl (15 mL) over the course of 20 minutes. Thereaction was stirred at reflux temperature for 4 hours. The PhCl layer wasdecanted and to the PPA-layers there was added toluene (50 mL) and stirring wascontinued for 10 minutes. The toluene layer was decanted and the procedurerepeated one more time. The decanted organic layers were evaporatedunder reduced pressure and redissolved in EtOAc (100 mL). The organic layer waswashed with saturated aqueous NaHCOTo a stirred soiution of PPA (42.22 g) in chiorobenzene (100 mL) was added soiution of (2- bromophenyi)(2, 2-diethoxyethyi)suifane (26.2 g, 86.185 mmoi) in chiorobenzene (20 mL) dropwise at 130 °C and aiiowed the reaction mass to stirred for 4 h. After compietion of reaction thereaction mixture was cool down to room temperature and decants the organic layer and keeps it aside. The residue was extracted with toluene (3 x 100 mL) and combined organic layers were evaporated under reduced pressure to give crude mass which was purified by column chromatography on silica gel using 2percent ethyl acetate/hexane as eluent to afford 7- bromobenzo[b]thiophene (12.7 g, 59.62 mmol) as colorless liquid. ‘H-NMR (400 MHz, CDC13):o 7.76 (dd, J’ = 8.2 Hz, J” = 0.9 Hz, 1H), 7.50-7.47 (m, 2H), 7.42 (d, J= 5.5 Hz, 1H), 7.23 (t, J=7.8 Hz, 1H).To a 500 ml 3-neck flask was weighed out 15 g of polyphosphoric acid (PPA) followed by chlorobenzene (250 ml). After the mixture was heated to reflux (2- bromo-phenylsulfanyl) -acetaldehyde DIMETHYLACETAL (8. 0g in 60 ml chlorobenzene, 28.9 mmol) was added dropwise over 2.5 h via addition funnel and refluxed for an additional 24 h. After the reaction cooled it was filtered through a silica plug and concentrated to 6.04 g amber colored oil. Further purification by column chromatography (100percent hexanes) afforded 5.47 g (89percent) product as a clear oil: 1H NMR (300 MHz, DMSO-D6) : 8 7. 37 (1H, t, J = 7. 8 HZ), 7.63 (2H, m), 7.90 (1H, d, J = 5. 5 HZ), 7.94 (1H, d, J = 7. 9 Hz). Anal. for CGHSBRS : Calc'd: C: 45.09 H: 2.36 Found: C: 45.41 H: 2.37Polyphosphoric acid (PPA) (100 g) was added to a stirring solution of l-bromo-2-((2, 2-dimethoxyethyl)sulfanyl)benzene (220 g, 0.84 mol, from Step 1) and toluene (2.2 L) at room temperature, and then the reaction mixture was heated at 110 °C. After 12 h, the reaction mixture was cooled to room temperature and then partitioned between water and ethyl acetate. The layers were separated, the organic material was washed sequentially with water and brine, dried (sodium sulfate), filtered, and the filtrate was concentrated under a vacuum. The residue was subjected to flash chromatography on silica gel (49: 1 hexane-ethyl acetate) to give 7-bromo-l-benzothiophene (82 g) as a colorless liquid.A mixture 3a or 4b (0.5 mmol), Ag2CO3 (0.05 mmol), AcOH(0.025 mmol) in DMSO (1.0 mL)was stirred at 120 °C. After 16 h, thereactionwas cooled down to room temperature and quenched with1 M hydrochloric acid solution (2 mL) and the aqueous phaseextracted with ethyl acetate. The combined organic layers werewashed with brine and dried sodium sulfate, filtered, and the solventswere removed under reduced pressure to give analyticallypure 4a or 4b.

Molecular Weight:213.10
XLogP3:3.6
Hydrogen Bond Acceptor Count:1
Exact Mass:211.92953
Monoisotopic Mass:211.92953
Topological Polar Surface Area:28.2
Heavy Atom Count:10
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes