Thionyl Chloride → 6-(3-Chloropropyl)-5,11-dioxo-11H-inde no[1,2-c]isoquinoline

Participants

Reaction Steps

Thionyl chloride (2 mL) was added to a solution of cis-4-carboxy-N-(3-chloropropyl)-3,4-dihydro-3-(4-methoxyphenyl)-1(2H)isoquinolone (8a) (0.510 g, 1.364 mmol) in benzene (40 mL). The reaction mixture was heated at reflux for 30 min, allowed to cool to room temperature, and concentrated. The residue was diluted with nitrobenzene (20 mL), chilled in an ice bath, and aluminum chloride (0.364 g, 2.728 mmol) was added. The reaction mixture was removed from the bath and heated at 100° C. for 1.5 h. Ice water (100 mL) was added and the solution was extracted with CHCl3 (3×50 mL). The combined organic layer was washed with sat NaHCO3 (3×50 mL), sat NaCl (50 mL), and dried over sodium sulfate. The solution was concentrated, hexanes (250 mL) were added, and liquid was decanted. The obtained solid was washed with hexanes (100 mL) and the liquid was again decanted. The solid was purified by flash column chromatography (SiO2), eluting with chloroform, to provide a purple-red solid (0.082 g, 17%) that was precipitated from EtOAc/hexanes: mp 195-198° C. IR (KBr) 1662, 1611, 1505, 1481, 1432, and 1299 cm−1; 1H NMR (CDCl3) δ 8.67 (d, J=8.1 Hz, 1 H), 8.31 (dd, J=8.2 Hz and 0.7 Hz, 1 H), 7.73 (m, 1 H), 7.66 (d, J=8.4 Hz, 1 H), 7.45 (m, 1 H), 7.22 (d, J=2.6 Hz, 1 H), 6.86 (dd, J=8.4 Hz and 2.6 Hz, 1 H), 4.67 (m, 2 H), 3.89 (s, 3 H), 3.83 (m, 2 H), 2.43 (m, 2 H); CIMS m/z (rel intensity) 354/356 (MH+, 100/30). Anal. (C20H16ClNO3) C, H, N.

Provenance & Evidence