Hydrochloric Acid → 7-Cyano-1,2,3,4-tetrahydroisoquinoline

Participants

Reaction Conditions

Reaction Steps

Hydrochloric acid (30.6 ml; 2 equiv.) was added at 0° C. to a solution of 1,2,3,4,-tetrahydroisoquinoline-7-amine (15.3 g; 1 equiv.) in 40 ml of water, and the reaction mixture was stirred for 10 minutes at −5° C. Sodium nitrate solution (7.13 g of sodium nitrate in 35 ml of water) was added dropwise at 0° C. in the course of 30 minutes, and the resulting reaction mixture was stirred for 30 minutes at 0° C. Finally, urea (1.86 g; 0.3 equiv.) was added. A mixture of sodium hydroxide solution (10.3 g of NaOH in 70 ml of H2O), potassium cyanide solution (33.5 g (5 equiv.) of KCN in 50 ml of H2O) and 76.5 ml of benzene was cooled to 0° C.; a nickel sulfate solution (32.6 g (1.2 equiv.) of NiSO4*6H2O in 50 ml of H2O) was added slowly, and stirring was carried out for 30 min. at 0° C. The diazonium solution was slowly added dropwise at 0° C., and the resulting reaction mixture was stirred first for 2 h at room temperature and then for 1 h at 50° C. When the conversion was complete, the mixture was cooled to 0° C., adjusted to a pH value of 8-9 with sodium hydroxide solution and filtered over Celite, and the filter cake was then washed with dichloromethane. The aqueous solution was extracted 3 times with dichloromethane. The combined organic phases were dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 10% methanol/chloroform). 1,2,3,4-Tetrahydroisoquinoline-7-carbonitrile (4 g; 24.5%) was obtained in the form of a solid.

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