Nitric Acid → 2-Nitroquinoline

Participants

Reaction Conditions

Reaction Steps

Quinoline (Formula (1), 12.9 g, 0.10 mole) was added dropwise over 5 min. with good agitation to a solution of 50 mL of concentrated sulfuric acid in a 250 mL round bottom flask. No attempt was made to control the exotherm and on this scale the final temperature was 77° C. The mixture was heated to 100° C. and 71% nitric acid (13.3 g, d. 1.42, 9.4 mL, 0.15 mole) was added at such a rate to keep the temperature between 100° C. and 110° C. Stirring was continued for an additional 30 minutes or until an HPLC (Zorbax® SB-C18 HPLC column, from Mac-Mod Analytical, Inc. of Chadds Ford, Pa. U.S.A.; dimensions 4½ mm (inside diameter) by 25 cm (length); HPLC conditions: 40:60 acetonitrile:water-0.5% ammonium acetate, 220 nm, flow 0.5 mL/min.) sample showed the reaction was complete. The mixture was cooled slightly and poured onto a mixture of 200 mL methylene chloride and 300 mL (by volume) of ice. The two phase mixture was placed in an ice bath and the temperature was kept below 25° C. while the pH was increased to 10 with concentrated ammonium hydroxide. The mixture was vacuum filtered through paper and transferred to a separatory funnel. The lower organic phase was separated and the aqueous layer was extracted with an additional 100 mL of methylene chloride. The combined organic layers were dried over magnesium sulfate, filtered and evaporated affording 15.8 g (91% yield) of a clear light amber oil which crystallized on standing. HPLC Analysis was conducted for 5-nitroquinoline and 8-nitroquinoline only: 45% 8-nitroquinoline (Formula (3), rt 9.0 min.) and 55% 5-nitroquinoline (Formula (2), rt 12.8 min).

Provenance & Evidence