Synthesis of novel bis(dihydropyridine) and terpyridine derivatives

Abstract

A synthesis of novel bis(cyanopyridones) by the reaction of the appropriate bis(cyanoacetamide) with the corresponding arylidenmalononitrile in the presence of basic catalysts was reported. In some cases, the corresponding bis(2-cyano-3-arylacrylamide) derivatives were isolated from these reactions as single products. The multicomponent strategy for the synthesis of the target compounds was also investigated. The utility of bis(cyanoacetamides) as building blocks for novel bisquinolinones was also studied.

Novel Bis(2‐cyanoketene‐S,S‐/S,N‐acetals): Versatile Precursors for Novel Bis(aminopyrazole) Derivatives

“…Using a similar approach, bis(5‐amino‐3‐(phenylamino)‐1 H ‐pyrazole‐4‐carboxamides) 10a and 10b , in which the pyrazole moieties are linked to benzene core via carbamoyl linkage, can be obtained in good yield. Thus, reaction of N , N′ ‐(1,ω‐phenylene)bis(2‐cyanoacetamide) 7 with phenylisothiocyanate 2 in KOH‐EtOH gave the corresponding potassium 3,3′‐(1,ω‐phenylenebis(azanediyl))bis(2‐cyano‐3‐oxo‐1‐(phenylamino)prop‐1‐ene‐1‐thiolate) derivatives 8 in high yield. Alkylation of the latter compounds with methyl iodide yielded the corresponding novel N , N ′‐(1,ω‐phenylene)bis(2‐cyano‐3‐(methylthio)‐3‐(phenylamino)acrylamides) 9a and 9b in 68 and 85% yields, respectively.…”

“…Encouraged by the aforementioned results, our study was extended to expand the scope of this reaction to prepare bis(pyrazole) 14 in which the pyrazole moieties are linked to pyridine core via carbamoyl linkage. Thus, reaction of N , N′ ‐(pyridine‐2,6‐diyl)bis(2‐cyanoacetamide) 11 with phenylisothiocyanate 2 in KOH‐EtOH gave the corresponding potassium 3,3′‐(pyridine‐2,6‐diylbis(azanediyl))bis(2‐cyano‐3‐oxo‐1‐(phenylamino)prop‐1‐ene‐1‐thiolate) 12 in high yield. Alkylation of the latter compound with methyl iodide yielded the corresponding novel N , N′ ‐(pyridine‐3,5‐diyl)bis(2‐cyano‐3‐(methylthio)‐3‐(phenylamino)acrylamide) 13 .…”

Synthesis of heterocyclic compounds via Michael and Hantzsch reactions

“…On the other hand, the formation of bis(pyridines) 51 linked via aromatic core was achieved by the reaction of [63] (Continues) bis-cyanoacetamide 50 with benzylidenemalononitrile derivatives 45 in ethanol in the presence of piperidine as catalyst (Scheme 23). [80] Compounds 51 were also obtained in good to excellent yields via a three-component reaction of two equivalents of both arylaldehyde 1 and malononitrile 2 with one equivalent of bis-cyanoacetamides 50 in ethanol in the presence of piperidine as a catalyst (Scheme 24). [80] Similarly, the reaction of bis-cyanoacetamide 52 linked to pyridine core with benzylidenemalononitrile derivatives 45 in dioxane in the presence of piperidine as 24%-85% Navarrete-Encina et al [70] a catalyst gave 6,6 00 -diamino-2,2 00 -dioxo-4,4 00 -diaryl-2H, 2"H-[1,2 0 :6 0 ,1 00 -terpyridine]-3,3 00 ,5,5 00 -tetracarbonitriles 53 in good yields (Scheme 25).…”

“…[80] Compounds 51 were also obtained in good to excellent yields via a three-component reaction of two equivalents of both arylaldehyde 1 and malononitrile 2 with one equivalent of bis-cyanoacetamides 50 in ethanol in the presence of piperidine as a catalyst (Scheme 24). [80] Similarly, the reaction of bis-cyanoacetamide 52 linked to pyridine core with benzylidenemalononitrile derivatives 45 in dioxane in the presence of piperidine as 24%-85% Navarrete-Encina et al [70] a catalyst gave 6,6 00 -diamino-2,2 00 -dioxo-4,4 00 -diaryl-2H, 2"H-[1,2 0 :6 0 ,1 00 -terpyridine]-3,3 00 ,5,5 00 -tetracarbonitriles 53 in good yields (Scheme 25). [80] Sanad et al [81] reported a synthesis of bis(6-amino-1, 2-dihydropyridine-3,5-dicarbonitriles) Khan et al [82] and Khurana et al [83] developed efficient methods for the synthesis of tetrahydro-cyclopenta[b] pyrans 57 by the reaction of aldehydes 1, malononitrile 2, and cyclopenta-1,3-dione 56 in different basic media (Scheme 27, Table 5).…”

N-(Thieno[2,3-b]pyridin-3-yl)cyanoacetamides: synthesis and cyclizations

“…1-(Cyanoacetyl)-3,5-dimethylpyrazole 1 is very cheap, handy and preparatively easily accessible from acetylacetone and cyanoacethydrazide. It was suggested as a better alternative to most of the cyanoacetylating agents in reactions with nitrogen nucleophiles and for various heterocyclization processes [8][9][10][11][12]. Pyrazole 1 reacts with a variety of amines, including heterocyclic amines [7].…”