[Synthesis]
The general procedure for the synthesis of 1,4-dichloroisoquinoline from 4-chloro-1(2H)-isoquinolinone was as follows: 4-chloro-2H-isoquinolin-1-one (3.1 g, 17 mmol) was dissolved in phosphorus trichloride (POCl3, 20 mL), and the reaction was carried out at reflux for 4 hours. After completion of the reaction, it was cooled to room temperature and concentrated under reduced pressure. The residue was extracted with chloroform (CHCl3, 50 mL) and neutralized with 1N sodium hydroxide (NaOH) solution. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate (MgSO4) and subsequently concentrated under reduced pressure to remove the solvent. The crude product was purified by fast column chromatography (Biotage Flash 40M) with hexane solution of 5% ethyl acetate (EtOAc) as eluent, resulting in the target product 1,4-dichloroisoquinoline (2.3 g, 66% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3) and mass spectrometry (MS): 1H NMR δ ppm 7.77 (ddd, J = 8.31, 7.09, 1.22 Hz, 1H), 7.88 (ddd, J = 8.31, 7.09, 1.22 Hz, 1H), 8.23 (d, J = 8.31 Hz, 1H), and 8.34 (s, 1H), 8.36 (d, J = 8.56 Hz, 1H); MS m/z 198 ([M + H]+). |