Ring transformations of 4H‐pyrans. Pyridines from 2‐amino‐4H‐pyrans

Abstract

Ring transformations of 4H‐pyrans into pyridines are reported. Treatment of 2‐amino‐4,6‐diaryl‐3,5‐dicyano‐4H‐pyrans (I) with nitrosylsulfuric acid brings about their transformation into 3,5‐dicyano‐4,6‐diaryl‐2‐pyridones (VI) which can also be obtained from α‐benzoylcinnamonitriles (IX) and cyanoacetamide. Similarly, 2‐amino‐4,6‐diaryl‐5‐carbethoxy‐3‐cyano‐4H‐pyrans (II) lead to 4,6‐diaryl‐5‐carbethoxy‐3‐cyano‐2‐pyridones (VII). Treatment of both series of pyrans with sulfuric acid results in the formation of the corresponding 3,4‐dihydro‐2‐pyridones (IV and V). Reaction of pyrans II with ammonium acetate in acetic acid yields 2‐amino‐4,6‐diaryl‐5‐carbethoxy‐3‐cyanopyridines (XII). Pyrans I undergo an entirely different type of reaction upon treatment with this reagent leading to 2,4,6‐triaryl‐3,5‐dicyano‐1,4‐dihydropyridines (XV).

Recent Developments in the Synthesis of Acetylcholinesterase Inhibitors

“…These pyridines have been described before and were readily prepared from the corresponding 4H-pyran-3-carboxylic acid derivatives (9, 10) [26] by reaction with ammonium acetate in glacial acetic acid. Compounds 7 and 8 showed spectroscopic data in good agreement with the reported compounds [20][21][22]. For the initial experiments and as well as in compounds 2 and 3, the selection of the substituents at the aromatic ring has been prompted by the easy availability of pyrans of the type (B) (Scheme 1) and by the anti-AChE activity observed for compound 2e (Scheme 1).…”

“…We have also addressed our attention to the analogous cycloannulated [1,8]naphthyridine ring system [18] (C) (Chart 1) in order to extend the Friedländer [19] reaction to the corresponding densely functionalized 6-amino-5cyanopyridines of type (D) [20][21][22] enable us to have a new set of compounds for the AChE inhibitory assays and to compare their pharmacology with compounds of type A (Chart 1) for structure-activity relationship purposes.…”

“…The synthesis of compounds 15 and 16 has also been accomplished via Friedländer condensation [19] of 2-amino-3-cyano-4,5-diphenylthiophene (20) with cyclohexanone or cycloheptanone, as depicted in Scheme 4. Precursor 2amino-3-cyano-4,5-diphenylthiophene (20) was not known, and for its synthesis we have followed the method reported by Gewald for other related compounds [36,37].…”

“…Precursor 2amino-3-cyano-4,5-diphenylthiophene (20) was not known, and for its synthesis we have followed the method reported by Gewald for other related compounds [36,37]. Starting from commercial phenylacetophenone, malonodinitrile and sulfur, under mild basic catalysis (piperidine), product 20 was obtained in 26% yield.…”

Synthesis of Novel 1‐Pyrazolylpyridin‐2‐ones as Potential Anti‐Inflammatory and Analgesic Agents

“…It is important to emphasize that the presence of the nitrile group at the 3-position of the pyridone ring activates the methyl group at position 4. Condensation of the 4-methyl group of compound 4a with dimethylformamide-dimethylacetal (DMF-DMA) in xylene [8,9,11] produced the 4-enamine derivative 5. Treatment of 1 with 4-anisaldehyde afforded the aryli-dine 6 which was allowed to react in a Michael -addition fashion with cyanoacetamide or cyano-acetic acid hydrazide [12,13] [9].…”