Chemical Properties
YELLOWISH CRYSTALLINE LOW MELTING SOLID
Uses
2-Amino-6-methylpyridine is a reagent used in the identification of selective inhibitor for phosphatidylinositol 3-kinase (PI3Ka).
Description
2-amino-6-methylpyridine, a colorless organic crystalline solid, is a prominent candidate to be exploited for the manufacturing of valuable compounds with biological activity.
Application
2-Amino-6-methylpyridine (2A6MPy) can be used as an electron donor and reacts with the π-acceptors tetracyanoethylene (TCNE), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 2,4,4,6-tetrabromo-2,5-cyclohexanediene dione (TBCHD) to form a solid charge transfer molecule in chloroform at 25 ℃. complex (CT), and the chemical formulae of the solid CT complexes were [(2A6MPy)(TCNE)2], [(2A6MPy)2(DDQ)], [(2A6MPy)4(TBCHD)], respectively
[2].
Reactions
2-Amino-6-methylpyridine can be used as precursor for the construction of diversified valuable scaffolds, e.g., 5-methyl-2-phenyl-3H-imidazo[4,5-b]pyridine and 6-bromo-5-methyl-2-phenylthiazolo[4,5-b]pyridine. The nitration of this nucleus in the presence of H2SO4 can yield N-(6-methyl-5-nitropyridin-2-yl)nitramide. It is also an important precursor for the generation of N-linked aminopiperidine-based gyrase inhibitors where during the course of reactions bromination of this nucleus was performed. Importantly, the amino group can be replaced by different halogen atoms, i.e. F, Cl, Br, or even by a nitroso group. Additionally, the methyl group on an aromatic system can be modified to the routine functional groups like aldehyde and carboxylic acid, or even bromination can be performed on this particular carbon[1].
Synthesis
The general procedure for the synthesis of 2-bromo-6-methylpyridine from 2-bromo-6-methylpyridine was as follows: 2-bromo-6-methylpyridine (1.0 mmol), aqueous ammonia solution (28%, 1.5 mmol), cuprous iodide nanoparticles (0.02 mmol), ligand 4a (3.0 mmol) and acetonitrile (2 mL) were added to an oven-dried flask. The reaction mixture was stirred at room temperature for 12 h under argon protection. The reaction process was monitored by thin layer chromatography (TLC). After completion of the reaction, the product was extracted with ether (5 x 5 mL). The organic layers were combined, washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography using mixed ethyl acetate-hexane solvent as eluent gave 2-amino-6-methylpyridine. All the products are known compounds and their structures were confirmed by 1H NMR, 13C NMR and mass spectrometry, see Supplementary Material for detailed data.
Purification Methods
Crystallise it three times from acetone and dry it under vacuum at ca 45o. Alternatively, keep it in contact with NaOH pellets for 3hours, with occasional shaking, decant and fractionally distil it [Mod et al. J Phys Chem 60 1651 1956]. It also recrystallises from CH2Cl2 on addition of pet ether. [Marzilli et al. J Am Chem Soc 108 4830 1986, Beilstein 22/9 V 210.]
References
[1] Ali A, et al. 2-Amino-6-methylpyridine based co-crystal salt formation using succinic acid: Single-crystal analysis and computational exploration. Journal of Molecular Structure, 2021; 1230: 129893.
[2] SHERZOD MADRAHIMOV . Electronic, infrared, mass spectrometry and thermal studies on the reaction of 2-amino-6-methylpyridine with π-acceptors[J]. Journal of Molecular Structure, 2020. DOI:10.1016/j.molstruc.2019.127021.
