Ethanol → HCID 19601657, compound

Participants

Reaction Steps

A mixture of 1-(3-iodophenyl)-3-methylisoquinoline (5.733 g, 16.62 mmol), N-bromosuccinimide (NBS) (7.399 g, 41.57 mmol), and benzoyl peroxide (BPO) (0.48 g) in CCl4 (100 mL) was heated to reflux while being illuminated by a flood lamp for 5 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was washed with saturated NaHCO3 aqueous solution (40 mL), dried (Na2SO4), then filtered. The filtrate was concentrated in vacuo, thereby affording crude 1-(3-iodophenyl)-3-dibromomethylisoquinoline (8.327 g) as a yellow oil. It was used directly in next step without any purifications. To a refluxing solution of crude dibromide (8.327 g) in EtOH (110 mL) and THF (60 mL) was added dropwise a solution of AgNO3 (7.994 g) in H2O (10 mL). The mixture was refluxed for 1 h and filtered while hot. The filter cake was washed with hot THF (2×30 mL). The combined filtrate was concentrated in vacuo to give crude 1-(3 -Iodophenyl)-3-isoquinoline-carboxaldehyde as an dark yellow oil (11.62 g, containing H2O). This oil was used without further purification. To a solution of crude aldehyde (11.62 g) in absolute EtOH (80 mL)was slowly added a solution of AgNO3 (7.28 g) in H2O (10 mL). To this stirred solution was added dropwise a solution of NaOH (5.80 g) in H2O (100 mL). The resulting black slurry was stirred at room temperature for 2 h. Then the mixture was filtered through a small Celite column. The filter cake was washed with ether. The ether was evaporated and the aqueous solution was made slightly acidic with concentrated HCl. The precipitate was collected by filtration, then washed with H2O. It was recrystallized from CH3CN, thereby affording 1-(3-iodophenyl)-3-isoquinolinecarboxylic acid as a yellow crystalline (2.22 g, 36%). mp 145-146° C. 1H NMR (DMSO-d6) d 7.37 (t, J=6.0 Hz, 1 H, aromatic), 7.65-7.71(m, 2 H, aromatic), 7.80 (t, J=4.8 Hz, 1 H, aromatic), 7.91 (d, J=6.6 Hz, 1 H, aromatic), 7.95 (d, J=6.3 Hz, 1 H, aromatic), 8.01 (s, 1 H, aromatic), 8.14 (d, J=6.0 Hz, 1 H, aromatic), 8.44 (s, 1 H, aromatic). HRMS Calcd for C16H10INO2 : 374.9756. Found: 374.9741.

Provenance & Evidence