Synthesis
General procedure for the synthesis of 3-aminoethylthiophene from 3-thiophene acetonitrile: the synthesis was carried out according to the literature method. A rubber septum and stir bar were added to a pre-cooled and oven-dried 25 mL round-bottomed flask under argon protection, followed by the addition of anhydrous InCl3 (0.681 g, 3.079 mmol), anhydrous THF (10 mL) and NaBH4 (0.341 g, 9.014 mmol). The reaction mixture was stirred at 25 °C for 1 h. Then 3-thiophene acetonitrile (0.340 mL, 2.981 mmol) was slowly added dropwise and stirring was continued for 16 h at 25 °C. Upon completion of the reaction, the reaction was quenched with 10 mL of 2.8 M hydrochloric acid solution and the mixture was refluxed for 2 hours to dissolve the residual metal salt. After cooling to 25 °C, 5 mL of methanol was added and refluxed again for 2 hours. The reaction mixture was cooled to 25 °C, filtered and the filtrate was evaporated to remove the methyl borate and methanol. The remaining acidic aqueous solution was extracted with DCM (3 x 10 mL) and the organic layer was discarded. The acidic aqueous layer was adjusted to pH ≈ 11 with NaOH pellets and extracted again with DCM (3 × 10 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and the solvent evaporated in vacuum to give 2-(3-thienyl)ethylamine as a yellow oil (0.250 g, 67% yield).1H NMR (300 MHz, CDCl3) data were as follows: δ = 7.20-7.30 (m, 1H, ArH), 7.00 (m, 1H, ArH), 6.95 (m. 1H, ArH), 2.96 (t, 2H, J=6.6 Hz, CH2), 2.78 (t, 2H, J=6.6 Hz, CH2), 1.45 ppm (bs, 2H, NH2).The 1H NMR spectra were in agreement with the literature reports.
References
[1] Journal of Organic Chemistry, 2012, vol. 77, # 1, p. 221 - 228
[2] Tetrahedron Letters, 2013, vol. 54, # 45, p. 6087 - 6089
[3] MedChemComm, 2015, vol. 6, # 9, p. 1679 - 1686
[4] Journal of the American Chemical Society, 1954, vol. 76, p. 4466
[5] Journal of the American Chemical Society, 1951, vol. 73, p. 351
