Synthesis of Z-2-methyl-6-R-1,2,3,4-tetrahydro-4-quinolinecarboxylic acids

Abstract

The known methods of reduction of quinolinecarboxylic acids not always give high yields of 1,2,3,4-tetrahydroquinolinecarboxylic acids and often involve a formation of product mixtures [1, 2]. We discovered an effi cient procedure for the synthesis of 2-methyland 2,6-dimethyl-1,2,3,4-tetrahydro-4quinolinecarboxylic acids (I and II). 2-Methyl-1,2,3,4-tetrahydroquinoline-4-carboxylic acid (I). To a solution of 2 g (0.01 mol) of 2-methylquinoline-4-carboxylic acid in 10 ml of 10% sodium hydroxide was added by small portions at stirring within 1 h 1.6 g of Raney alloy, and the mixture was stirred for 1 h more at room temperature. The precipitate was fi ltered off, washed with hot water, formic acid was added to the fi ltrate to pH 3, and the reaction product was extracted into chloroform and dried over anhydrous sodium sulfate. Chloroform was evaporated to dryness, and the residue was recrystallized from 50% ethanol. Yield 1.6 g (80%), colorless crystals, mp 131–134°C. IR spectrum, ν, cm–1: 1701 (CO), 2966 (CH3), 3278 (NH). 1H NMR spectrum, δ, ppm: 1.29 d (3H, CH3, J 6.11 Hz), 2.01 d.d (1H, H3a, J 12.21, 10.98 Hz), 2.26 d.d.d (1H, H3e, J 10.98, 6.11, 2.44 Hz), 3.45 d.d.d (1H, H2a, J 10.98, 6.11, 2.44 Hz), 4.01 d.d (1H, H4a, J 12.21, 6.11 Hz), 6.56 d (1H, H8, J 7.33 Hz), 6.71 t (1H, H6, J 7.33 Hz), 7.07 t (1H, H7, J 7.33 Hz), 7.14 d (1H, H5, J 3.33 Hz). Mass spectrum, m/z (Irel, %): 205 (44) [M]+, 190 (28), 146 (91), 130 (100), 118 (9.5), 103 (4), 77 (19), 65 (8). Found, %: C 69.00; H 6.87; N 7.40. C11H13NO2. Calculated, %: C 69.11; H 6.80; N 7.33. 2,6-Dimethyl-1,2,3,4-tetrahydroquinoline-4carboxylic acid (II) was prepared similarly. Yield 85%, mp 136–140°C (50% ethanol). IR spectrum, ν, cm–1: 1716 (CO), 2950, 2854 (CH3), 3382 (NH). 1H NMR spectrum, δ, ppm: 1.29 d (3H, CH3, J 6.3 Hz), 1.8 d.d (1H, H3a, J 12.3, 11.1 Hz), 2.11 s (3H, CH3), 2.2 d.d.d (1H, H3e, J 11.3, 7.11, 2.6 Hz), 3.35 d.d.d (1H, H2a, J 11.11, 6.58, 2.4 Hz), 3.85 d.d (1H, H4a, J 12.5, 6.6 Hz), 6.4 d (1H, H8, J 8.1 Hz), 6.8 d (1H, H7, J 8.33 Hz), 7.4 s (1H, H5). Mass spectrum, m/z (Irel, %): 219 (45) N