Improved Synthesis of Mono- and Disubstituted 2-Halonicotinonitriles from Alkylidene Malononitriles was written by Longstreet, Ashley R.;Campbell, Brian S.;Gupton, B. Frank;McQuade, D. Tyler. And the article was included in Organic Letters in 2013.Application In Synthesis of 2-Chloro-4-methylpyridine-3-carbonitrile This article mentions the following:
Pyridines with 2,3,4 and/or 5 substitution remain challenging to prepare Existing strategies to form multisubstituted 2-halonicotinonitriles via enamines suffer from dimerization of the starting alkylidene malononitriles resulting in low yields. Through alteration of reaction conditions, a new high yielding method into enamines was realized by condensing DMF-DMA and alkylidene malononitriles in the presence of substoichiometric acetic anhydride. Cyclization of the resulting enamines under Pinner conditions provided 2-halonicotinonitriles, e.g., I, in high overall yields. In the experiment, the researchers used many compounds, for example, 2-Chloro-4-methylpyridine-3-carbonitrile (cas: 65169-38-2Application In Synthesis of 2-Chloro-4-methylpyridine-3-carbonitrile).
2-Chloro-4-methylpyridine-3-carbonitrile (cas: 65169-38-2) belongs to pyridine derivatives. Pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJ·mol−1 in pyridine vs. 150 kJ·mol−1 in benzene). Reduced pyridines, namely tetrahydropyridines, dihydropyridines and piperidines, are found in numerous natural and synthetic compounds. The synthesis and reactivity of these compounds have often been driven by the fact many of these compounds have interesting and unique pharmacological properties. Application In Synthesis of 2-Chloro-4-methylpyridine-3-carbonitrile