5-Chlorobenzothiophene

Chemical Properties

White solid

Uses

5-Chlorobenzo[b]thiophene is used as pharmaceutical intermediate.

Synthesis

To a 25 mL round-bottomed flask was added (4-chlorophenyl)(2,2-diethoxyethyl)thiane (500 mg, 1.92 mmol) and chlorobenzene (2 mL). The resulting mixture was added dropwise to a boiling solution of chlorobenzene (5 mL) in polyphosphoric acid (1 g) over 5 min. After completion of the reaction, the mixture was slowly poured into ice water (25 mL) and extracted three times with ethyl acetate (25 mL). The organic phases were combined, washed with saturated saline (50 mL) and dried over anhydrous sodium sulfate. The organic phases were concentrated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography, using petroleum ether as eluent, to give 5-chlorobenzothiophene (290 mg, 90% yield) as an off-white solid.

References

[1] Patent: US2008/21026, 2008, A1. Location in patent: Page/Page column 17; 27
[2] Patent: CN103896967, 2016, B. Location in patent: Paragraph 0048; 0052-0054
[3] Journal of Organic Chemistry, 1995, vol. 60, # 7, p. 1936 - 1938
[4] Phosphorus, Sulfur and Silicon and the Related Elements, 1994, vol. 96, # 1-4, p. 441 - 444
[5] Bioorganic and medicinal chemistry, 2004, vol. 12, # 9, p. 2251 - 2273