Cyanation of amine oxide salts. A new synthesis of cyanopyridines was written by Feely, Wayne E.;Beavers, Ellington M.. And the article was included in Journal of the American Chemical Society in 1959.Safety of 4-Methylpicolinonitrile This article mentions the following:
In general, pyridines, quinolines, and isoquinoline oxidized with 30% H2O2 in AcOH according to Ochiai (C.A. 48, 3359i) gave the corresponding amine oxides, which without purification, treated slowly at room temperature with an equimolar quantity of Me2SO4 and the mixture heated 2 hrs. on a steam bath gave the N-OMe MeSO4– salts (for example, 1-methoxy-2-methylpyridinium methyl sulfate, m. 57-60°, and its 6-Me derivative, m. 95-7°), and these without purification added in aqueous solution to KCN in H2O gave the cyano derivatives, isolated by filtration (F), distillation (D), recrystallization (R), steam distillation (SD), or extraction with CHCl3 (E) (product, m.p., % yield, method of isolation, m.p. of picrate given): 4-NCC5H4N (I), 80-2°, 32, E or D or R, 200-3°; 2-NCC5H4N (II), 22-5°, 49, -, -; 2,6-NCC5H3NMe, 71-3°, 48, F or R, 105-8°; 4,2-NCC5H3NMe, 46-8°, 10, -, -; 2,4-NCC5H3NMe, 89-91°, 40, F or R, 100-2°; 2,3-NCC5H3NMe, 87-90°, 36, F or R, 93-5°; 2,5-NCC5H3NMe, 73-5°, 6, -, -; 4,3-NCC5H3NMe, 51-2°, 6, -, -; 2,4,6-NCC5H2NMe2, 55-6°, 73, E or D, 100-2°; 4,2,6-NCC5H2NMe2, 77-81°, 40, F or E or D, 178-81°; 2,4-(NC)2C5H3N, 88-91°, 54, F or R, -; 2-cyanoquinoline, 94-6°, 93, F or R, -; 2-cyano-4-methylquinoline, 96-8°, 65, F or R, -; 4-cyano-2-methylquinoline, 105-6°, 7.2, SD, -; 1-cyanoisoquinoline, 92-3°, 95, F or R, -. Three methods are described for the preparation of I. C5H5N(O) (III) (0.25 mole) refluxed 12 hrs. with 0.25 mole C9H19I in 200 ml. MeCN and the mixture then cooled in ice yielded 55% (C5H5NOC9H19)I, yellow needles, m. 87-90°. This (0.1 mole) added slowly to 0.3 mole KCN in 150 ml. H2O, the oily product extracted with ether, and the ether solution extracted with 10% HCl yielded from the ether layer 75% C9H19OH, b. 210-15°, n20D 1.4328; phenylurethan m. 62.5-3.5°. The aqueous acid layer neutralized with Na2CO3 and extracted with ether yielded 42% I; HCl salt m. 244-7° (decomposition). Also III (0.5 mole) similarly refluxed with 0.2 mole I(CH2)10I gave [C5H5NO(CH2)10ONC5H5]2I, m. 118-20° (decomposition), and this similarly treated with KCN gave a solid instead of an oil, filtered without ether extraction, 82% HO(CH2)10OH, m. 72-4° (diacetate m. 23-6); from the filtrate was extracted with ether 37% I. Also (C5H5NOMe)MeSO4 (0.5 mole) in 125 ml. H2O added during 1 hr to 1.5 mole NaCN in 250 ml. H2O at -5°, the mixture kept 1 addnl. hr. at -5°, stirred 3 hrs. at 20°, extracted with CHCl3, and the residue from the extract distilled yielded 16% I, b. 208-12°, and 49% II, b. 220-5°. The mechanism of the general reaction of CN– with such N-methoxy quaternary salts was discussed, in which the intermediate N-methoxy dihydro compound lost H+ and OMe– to reform the aromatic system. In the experiment, the researchers used many compounds, for example, 4-Methylpicolinonitrile (cas: 1620-76-4Safety of 4-Methylpicolinonitrile).
4-Methylpicolinonitrile (cas: 1620-76-4) belongs to pyridine derivatives. Pyridine’s the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.Safety of 4-Methylpicolinonitrile