Regioselective synthesis and properties of 3-cyano-6-methyl-4-trifluoromethylpyridine-2(1H)-thione. Molecular and crystal structure of 3-cyano-2-ethylthio-6-methyl-4-trifluoromethylpyridine

Abstract

The reaction of trifluoroacetylacetone with cyanothioacetamide proceeded regioselectively to form 3-cyano-6-methyl-4-tfifluoromethylpyridine-2(l/-/)-thione from which the corresponding 2-alkylthiopyridines and 3-aminothieno[2,3-b]pyridines were obtained. The crystal and molecular structure of 3-cyano-2-ethylthio-6-methyl-4-trifluoromethylpyridine was established by X-ray diffraction analysis.

Preparation of Trifluoromethylpyridine Libraries

“…The results of X-ray diffraction analysis of 3d and 4j are in agreement with the proposed regioselectivity of alkylation of 1 and 2 . , The structural parameters of 3d and 4j are typical of these types of compounds. , X-ray studies of 3d also showed substantial divergence of the ethyl group out of the plane of the heterocyclic ring. This conformation is probably affected by intramolecular nonvalence contacts between the nitrogen atom in the pyridine ring and an α-hydrogen or carbon atoms of the CH 3 CH 2 S− group.…”

“…Full details of the X-ray analysis of 3d and 4j were presented elsewhere. 23,24 Our experiments demonstrated that both S-alkyl derivatives 3a-s and 3-aminothieno[2,3-b]pyridines 4h-u can be produced in satisfactory yields using uniform conditions (see Experimental Section and Table 1). However, the best results can be achieved at optimal reaction times.…”

“…The results of X-ray diffraction analysis of 3d and 4j are in agreement with the proposed regioselectivity of alkylation of 1 and 2. 23,24 The structural parameters of 3d and 4j are typical of these types of compounds. 25,26 X-ray studies of 3d also showed substantial divergence of the ethyl group out of the plane of the heterocyclic ring.…”

“…Such flattening of the molecule is favored by the intramolecular hydrogen bonding. Full details of the X-ray analysis of 3d and 4j were presented elsewhere. , …”

“…Synthesis of 3d and 4j was reported previously. 23,24 3-Cyano-2-alkylthiopyridines (3a-s). General Procedure.…”