Methylpyridine derivatives. I. Synthesis of 4-substituted 3-picolines was written by Suzuki, Yasuyuki. And the article was included in Pharmaceutical Bulletin in 1957.Synthetic Route of C7H6N2 This article mentions the following:
The HCl salt of 3-picoline 1-oxide (16.5 g.) refluxed 5 h. with 30 cc. POCl3 in 30 cc. CHCl3, cooled, poured into ice H2O, the aqueous layer made alk. with Na2CO3, steam-distilled, the distillate saturated with NaCl, extracted with ether, and the extract distilled in vacuo gave 35.5% liquid (I), b30 77-80闂? and 28.3% liquid (II), b30 81-92闂? I (1 g.) yielded 2.24 g. picrate, m. 152-3闂? of the 4-Cl derivative (III) of 3-picoline (IV), identical with the picrate of deoxygenated 4-chloro-3-picoline 1-oxide (Itai and Ogura, C.A. 50, 1808g). II (2 g.) converted to the HO derivative by the method of Ochiai, et al. (C.A. 50, 991a), redistilled in vacuo, and chromatographed over Al2O3 yielded 0.46 g. 2-HO derivative of IV, m. 139-41闂?(picrate, m. 158-60闂? (cf. Seide, C.A. 19, 518), 0.3 g. 6-HO derivative of IV, m. 181-3闂?(picrate, m. 147-8闂? (cf. Bradlow and Vander Werf, C.A. 43, 9069b), and a small amount of 4-HO derivative of IV, b2 190-2闂? m. 96-8闂?(picrate, m. 205-6闂? (cf. Clemo and Swan, C.A. 42, 4581d). Therefore, II was a mixture of 2-, 4-, and 6-Cl derivatives of IV. III (25.7 g.) treated according to Ochiai and Suzuki (C.A. 50, 1015g) yielded 10.2 g. 4-cyano derivative (V) of IV, b80 130-2闂? m. 50-2闂?(picrate, m. 154-6闂?. V (4 g.) added dropwise in the cold to the Grignard reagent from 17.3 g. PhBr, 2.6 g. Mg, 50 cc. absolute ether, and a trace of iodine, stirred an addnl. 30 min. at room temperature, the ether evaporated, the residue refluxed 2-3 h. with 50 cc. dry PhMe, cooled, saturated NH4Cl solution added, the organic layer extracted with 10% HCl, and the acid extract made alk. and extracted with ether yielded 4.38 g. 4-Bz derivative of IV, b3 140-3闂? picrate, m. 178-80闂? V (0.5 g.) refluxed 3 h. on a H2O bath with 0.75 g. NaOH in 30 cc. 70% EtOH and worked up as usual yielded 0.3 g. 4-HO2C derivative of IV (3-methylisonicotinic acid), m. 234-6闂? Et ester (0.91 g. from 1 g. acid), b14 116-17闂?(picrate, m. 138-40闂?. In the experiment, the researchers used many compounds, for example, 4-Methylpicolinonitrile (cas: 1620-76-4Synthetic Route of C7H6N2).
4-Methylpicolinonitrile (cas: 1620-76-4) belongs to pyridine derivatives. Pyridine is diamagnetic and has a diamagnetic susceptibility of 闂?8.7 闂?10闂? cm3闁荤姾娅ｅΛ纭俵闂?.The molecular electric dipole moment is 2.2 debyes. The standard enthalpy of formation is 100.2 kJ闁荤姾娅ｅΛ纭俵闂? in the liquid phase and 140.4 kJ闁荤姾娅ｅΛ纭俵闂? in the gas phase. Pyridine derivatives are also useful as small-molecule 婵?helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Synthetic Route of C7H6N2