Sulfuric Acid → 7-Chloroisoquinolin-3-amine

Participants

Reaction Steps

In a flask was placed N-(3-chlorobenzyl)-2,2-diethoxyacetimidamide (1.9 g, 7.02 mmol) and sulfuric acid (14 mL, 263 mmol). This was stirred at room temperature for 24 hours. The reaction was then neutralized to pH 9 using 10 N NaOH. The resulting precipitate was dissolved in dichloromethane and the water layer was washed with dichloromethane. The organic layers were combined and concentrated to give the above regioisomers (1.1 grams, 6.1 mmol, 88%) in a 2:1 ratio of 7-chloroisoquinolin-3-amine to 5-chloroisoquinolin-3-amine. This regioisomer mixture is carried on without further separation. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.89 (s, 1H) 8.81 (s, 2H) 7.90 (d, J=2.26 Hz, 2H) 7.82 (d, J=8.28 Hz, 1H) 7.65 (dd, J=7.28, 1.00 Hz, 1H) 7.58 (d, J=9.03 Hz, 2H) 7.44 (dd, J=9.03, 2.26 Hz, 2H) 7.07-7.19 (m, 1H) 6.83 (s, 1H) 6.64 (s, 2H) 6.28 (s, 2H) 6.05 (s, 4H) LC/MS R.T=0.955 mins, [M+H]=181.03

Provenance & Evidence