Hydroxyamine hydrochloride → 4-Hexylthiophene-2-carbonitrile

A mixture solution of 4-hexylthiophene-2-carbaldehyde (11.8 g, 60.0 mmol) and hydroxylamine hydrochloride salt (6.3 g, 90 mmol) in pyridine/ethanol (60 mL, 1/1 v/v) was stirred at 80° C. overnight. Then the solvent was removed and the residue was dissolved in chloroform (100 mL). The solution was washed with distilled water (2×50 mL) and dried over anhydrous magnesium sulphate. The solvent was removed and the viscous liquid residue was refluxed in acetic anhydride (30 mL) containing potassium acetate (0.2 g) for 3 h. Then the mixture was poured into distilled water (100 mL) and extracted with hexanes (3×50 mL). The combined organic phase was washed three times with water (50 mL), dried over anhydrous magnesium sulfate before the solvent was removed by rotary evaporation. The yellow liquid residue was purified by silica-gel column chromatography (EtOAc/hexane=7/93, v/v, Rf=0.4) to yield a clear light yellow liquid product. (9.8 g, 84.5% yield). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.43 (d, 1H, J=1.4 Hz); 7.17 (d, 1H, J=1.4 Hz); 2.60 (t, 2H, J=8.0 Hz); 1.59 (m, 2H); 1.22-1.36 (m, 6H); 0.87 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 144.04, 138.22, 127.41, 114.48, 109.28, 31.45, 30.18, 29.86, 28.67, 22.46, 13.96. HRMS EI calcd for C11H15S 193.0925, found 193.0915.

1. customThen the solvent was removed
2. dissolutionthe residue was dissolved in chloroform (100 mL)
3. washThe solution was washed with distilled water (2×50 mL)
4. dry with materialdried over anhydrous magnesium sulphate
5. customThe solvent was removed
6. temperaturethe viscous liquid residue was refluxed in acetic anhydride (30 mL)
7. additioncontaining potassium acetate (0.2 g) for 3 h
8. additionThen the mixture was poured
9. distillationinto distilled water (100 mL)
10. extractionextracted with hexanes (3×50 mL)
11. washThe combined organic phase was washed three times with water (50 mL)
12. dry with materialdried over anhydrous magnesium sulfate before the solvent
13. customwas removed by rotary evaporation
14. customThe yellow liquid residue was purified by silica-gel column chromatography (EtOAc/hexane=7/93, v/v, Rf=0.4)
15. customto yield a clear light yellow liquid product

ORD record

ord-7205a3770dcc4e36bd851ac41d8cbcc3

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08673183B2