8-Hydroxyquinoline, ACS Reagent, 99%, Sigma Aldrich 

Hydrogen peroxide solution, 35 wt.% in H₂O, Sigma Aldrich

Sodium tungstate dihydrate, ACS reagent, 99%, Sigma Aldrich

Methanol, commercial grade

To a stirred solution of 100.0 g (0.69 mol) of 8-hydroxyquinoline in 1500 mL of methanol, the solution of 5.0 g Na₂WO₄^.2H₂O (5% of catalyst based on the weight of  8-hydroxyquinoline) in 30 mL of water was added. Then 500 mL of 35% H₂O₂ (5.82 mol) was added with agitation at 20–25^oC for 2 h. When the addition was complete the reaction was kept at ambient temperature until TLC analysis of a sample showed almost complete conversion of 8-hydroxyquinoline (approximately 54 h). Slightly yellow mixture was poured into 1000 mL of water. The resulting mixture was allowed to stand at ambient temperature for 12–15 h and then at –30 ^oC for 7 h. Crystalline product was filtered off, washed with cold water (5 x 200 mL) and dried at 50 ^oC to give 99.5 g (89,6% yield) of 8-hydroxyquinoline-1-oxide with purity of 99,9% (UPLC) and melting point of 138–140 ^oC.

8-Hydroxyquinoline-1-oxide may also be obtained by oxidation of 8-hydroxyquinoline with 35 % H₂O₂ in acetic acid, or by using 75–80% 3-chloroperbenzoic acid in CHCl₃, in yields of 48% and 74%, respectively. However, both of these procedures allow to obtain the 8-hydroxyquinoline-1-oxide with lower yield than that described by us. Moreover, in both cases, the product of oxidation requires purification by crystallization often using large amounts of solvents.

TLC (CHCl₃:MeOH = 100:3); R_f = 0.62.

 MS (ESI+); 162 [MH]⁺.

δ_H (300 MHz, CDCl₃) ppm; 7.03 (1H, d, J 7.9); 7.17–7.25 (2H, m); 7.46 (1H, t, J 8.1); 7.76 (1H, d, J 8.6); 8.21 (1H, d, J 6.0); 15.06 (1H, s).

H. E. Albert, P. G. Haines, Process for tertiary amine oxides and hydroxylamines, Patent US 3,274,252 (1966).

D. K. Johnson, S. J. Kline, 8-Hydroxyquinoline chelaqting agents, Patent US 5,021,567 (1991).

K. Ramaiah, V. R. Srinivasan, Studies i Heterocyclic N-oxides. Part III. 8-Hydroxyquinoline N-oxide, Proccedings of the Indian Academy of Sciences, Section A, 1962, 55, 360-366.

K. M. Beeh, J. Beier, Indacaterol, a Novel Inhaled, Once-Daily, Long-Acting Beta₂-Agonist for Treatment of Obstructive Airways Diseases, Advances in Therapy, 2009, 26:7, 691-699. DOI 10.1007/s12325-009-0044-3.