The product has been used in a Mn-catalyzed cross-coupling with aryl- and alkylmagnesium halides. It has also been used in a Pd-catalyzed cross-coupling with heteroaryl boronic acids and esters. Furthermore, it has been used in a homocoupling reaction to yield bis-isoquinoline, each enantiomer of which might be very useful as a chiral ligand for asymmetric synthesis. 1-Chloroisoquinone is used in the preparation of new aminoisoquinolinylurea derivatives which show antiproliferative activity against melanoma cell lines. It can also be applied to the control of storage age and stability of unstable boronic acids.
The general procedure for the synthesis of 1-chloroisoquinoline from isoquinoline-N-oxide was as follows: phosphoryl chloride (200 mL) was slowly added dropwise to isoquinoline-N-oxide (20.0 g) under ice bath cooling conditions. Subsequently, the reaction mixture was heated to 105 °C and refluxed overnight. Upon completion of the reaction, the excess phosphoryl chloride was removed by distillation under reduced pressure. The residue was quenched with ice water and extracted with dichloromethane. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography using a mixed solvent of ethyl acetate and petroleum ether as eluent to afford the target product 1-chloroisoquinoline (21.0 g, 85% yield). The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 8.25-8.31 (m, 2H), 8.08 (d, J = 8.0 Hz, 1H), 7.88-7.91 (m, 2H), 7.80-7.84 (m, 1H). Mass spectrometry (ESI+) showed a molecular ion peak m/z 164.0. HPLC analysis (Method A) showed a retention time (Rt) of 8.29 min and a purity of 96.0%.
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