8-hydroxy-2-methylquinoline-7-carboxylic acid synthesis

Yield:23051-08-3 59%

Reaction Conditions:

Stage #1: 2-methyl-8-quinolinolwith potassium tert-butylate in tetrahydrofuran; for 1 h;Reflux;
Stage #2: carbon dioxide in N,N-dimethyl-formamide at 115 - 120; for 3 h;

Steps:

8-Hydroxy-2-methylquinoline-7-carboxylic acid (2a)

General procedure: To the solution of 1a, 1b or 1c (100 mmol) in THF (200 mL), Bu^tOK was added (11.2 g, 100 mmol), respectively. The reaction mixture was vigorously stirred under reflux for an hour. The volatiles were evaporated and the residue was dissolved in dry DMF (100 mL) followed by heating the reaction mixture to 115 °C. Subsequently, dry CO₂ was passed through the reaction mixture for 3 h in the temperature range 115-120 °C. The reaction mixture was cooled down to room temperature and the residue was acidified by water solution of hydrochloric acid (1%), and was filtered off. The solid was dissolved in water solution of K₂CO₃ with further filtration. The water layer was acidified by water solution of hydrochloric acid (1%), and the solid was filtered. The crude product was dried over P₄O₁₀ and purified by extraction at Soxhlet apparatus (AcOEt). 8-Hydroxy-2-methylquinoline-7-carboxylic acid (2a) (yellow) 11.98 g (59 mmol, 59%), mp_dec. = 206-207 °C (lit. 206-208 °C [11]; ¹H NMR (DMSO-d₆; 400.1 MHz) δ = 2.80 (s, 3H, CH₃), 7.20 (d, J_HH = 8.6 Hz, 1H, aromatic), 7.69 (d, J_HH = 8.5 Hz, 1H, aromatic), 7.86 (d, J_HH = 8.6 Hz, 1H, aromatic), 8.52 (d, J_HH = 8.5 Hz, 1H, aromatic) [11]; ¹H NMR (Pyridine-d₅; 400.1 MHz) δ = 2.70 (s, 3H, CH₃), 7.29 (d, J_HH = 8.4 Hz, 1H, aromatic), 7.30 (d, J_HH = 8.7 Hz, 1H, aromatic), 8.01 (d, J_HH = 8.4 Hz, 1H, aromatic), 8.29 (d, J_HH = 8.6 Hz, 1H, aromatic); ¹H NMR (CF₃CO₂D; 400.1 MHz) δ = 3.49 (s, 3H, CH₃), 8.09 (d, J_HH = 8.8 Hz, 1H, aromatic), 8.35 (d, J_HH = 8.7 Hz, 1H, aromatic), 8.71 (d, J_HH = 8.8 Hz, 1H, aromatic), 9.26 (d, J_HH = 8.7 Hz, 1H, aromatic); ¹³C{¹H} NMR (DMSO-d₆; 100.5 MHz) δ = 22.6, 113.2, 113.4, 125.5, 128.0, 130.9, 135.5, 141.4, 156.9, 161.2, 171.2 [12]; ¹³C{¹H} NMR (Pyridine-d₅; 100.5 MHz) δ = 24.7, 112.9, 116.6, 124.2, 126.3, 130.6, 136.6, 139.8, 157.7, 161.2, 174.6; ¹³C{¹H} NMR (CF₃CO₂D; 100.5 MHz) δ = 19.7, 112.9, 118.7, 126.3, 128.7, 129.6, 131.3, 146.9, 152.5, 159.4, 173.0 [12]; CCDC 806597.

References:

Nycz, Jacek E.;Malecki, Grzegorz J. [Journal of Molecular Structure,2013,vol. 1032,p. 159 - 168]