4-Methylnicotinic acid

Chemical Properties

White powder

Uses

4-Methylnicotinic Acid is used in the synthesis of nicotinic acid substituted nicotinic acid adenine dinucleotide phosphate analogs.

Synthesis

General procedure for the synthesis of 4-methylpyridine-3-carboxylic acid from 3-cyano-4-methylpyridine: 3-cyano-4-methylpyridine (1.2 kg, 10.2 mol) was added to a mixture of sodium hydroxide (1.6 kg, 40.6 mol) and 70% aqueous ethanol solution (7.2 L). The reaction mixture was stirred under reflux conditions for 2 hours. After completion of the reaction, the mixture was cooled to room temperature and acidified by slow dropwise addition of concentrated hydrochloric acid (4.06 L). Subsequently, the solvent was removed under reduced pressure to give a white solid product. Ethanol (10 L) was added to the residue, heated to reflux and maintained for 10 min. After thermal filtration, ethanol was evaporated under reduced pressure at 20 mmHg to give 4-methylpyridine-3-carboxylic acid as a white solid (1.33 kg, 96% yield). Melting point: 215-216°C (literature value 215-217°C). IR (KBr, cm^-1): 2423 (O-H stretching vibration), 1721 (C=O stretching vibration). 1H NMR (DMSO-d6, 300 MHz): δ 11.9 (broad single peak, 1H, COOH), 9.00 (single peak, 1H, pyridine ring H), 9.00 (single peak, 1H, pyridine ring H). 8.72 (double peak, J = 4.9 Hz, 1H, pyridine ring H), 7.67 (double peak, J = 4.9 Hz, 1H, pyridine ring H), 2.67 (single peak, 3H, CH3).13C NMR (DMSO-d6, 75 MHz): δ 179.7 (COOH), 166.4, 153.9, 148.2, 147.6, 128.3 (pyridine ring C), 21.4 (CH3).MS (ESI): m/z 138.1 [M + H]+, 136.1 [M - H]-.

References

[1] Letters in Organic Chemistry, 2016, vol. 13, # 6, p. 450 - 452
[2] Tetrahedron, 2013, vol. 69, # 33, p. 6799 - 6803
[3] Journal of the American Chemical Society, 1944, vol. 66, p. 1456,1458
[4] Journal of the American Chemical Society, 1943, vol. 65, p. 2233,2235
[5] Canadian Journal of Chemistry, 1983, vol. 61, p. 2813 - 2820