6-Chloro-2,4-dimethylnicotinonitrile synthesis

Yield:101251-72-3 70%

Reaction Conditions:

with N-benzyl-N,N,N-triethylammonium chloride;N,N-dimethyl-formamide;trichlorophosphate

Steps:

EXPERIMENTAL

Our study is briefly described by Scheme 1. As is well known, Vilsmeier reagent (DMF/POCl3)can be used to dehydrate an amide group, convertingit into a nitrile group [2]. We transformed the amidegroup of pyridone (1) into a nitrile group (2) using thisapproach. The reaction mixture was refluxed for 5 hyielding a dark brown preparation. The product wasisolated via extraction in a Soxhlet apparatus withchloroform. A light yellow product was obtained witha yield of 52%.The next step was to obtain chloropyridine (3).Pyridone (2) was added to a mixture of DMF withPOCl3 and ref luxed for 5 h. After purification viacolumn chromatography, a white crystalline solid(as needles) was obtained with a yield of 62%.A similar method was used to obtain chloropyridine(1) without transforming the side amide groupinto a nitrile group. The reaction was conducted infreshly distilled POCl3 in the presence of triethylbenzylammoniumchloride to increase the concentrationof Cl- ions. Chloropyridine (3), however,was obtained instead of expected reactionproduct (4). The yield was 70%, higher than in twostepsynthesis.

References:

Koval’, Ya. I.;Okul’;Yatsenko;Babaev;Polyakova;Rybakov [Russian Journal of Physical Chemistry,2017,vol. 91,# 2,p. 246 - 251][Zh. Fiz. Khim.,2017,vol. 91,# 2,p. 247 - 252,6]