Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

Abstract

4-Aza-6-nitrobenzofuroxan (ANBF) reacts with 1,3-dicarbonyl compounds and other CH acids to give carbon-bonded 1,4-adducts – 1,4-dihydropyridines fused with furoxan ring. In the case of most acidic β-diketones, which exist mainly in the enol form in polar solvents, the reactions proceed in the absence of any added base emphasizing the highly electrophilic character of ANBF. The resulting compounds combine in one molecule NO-donor furoxan ring along with a pharmacologically important 1,4-dihydropyridine fragment and therefore can be considered as prospective platforms for the design of pharmacology-oriented heterocyclic systems.

Synthesis and Facile Dearomatization of Highly Electrophilic Nitroisoxazolo[4,3-b]pyridines

“…In 1 H NMR spectra of adducts 4, the signals corresponding to H(7) protons in the range of 5.0-5.5 ppm, as well as downfield signals of NH protons (9.8-10.4 ppm) and H(5) at 8.1 ppm, were observed as doublets with close coupling constants. This confirms the nucleophilic addition at position 7 and is consistent with the results obtained previously for other highly electrophilic azolopyridines [45,46,48].…”

“…It was found that nitro derivatives 3a-d react with all ranges of used nucleophiles under mild conditions (MeCN, room temperature, base-free), forming 1,4-addition products, 4a-m, Scheme 3. As in the case of A [45], β-dicarbonyl compounds react with 3 in enolic form. The reaction rate was similar to that of superelectrophiles A and B [45,46] (Scheme 1), thus indicating the high electrophilicity of isoxazolo[4,3-b]pyridine system.…”

“…As in the case of A [45], β-dicarbonyl compounds react with 3 in enolic form. The reaction rate was similar to that of superelectrophiles A and B [45,46] (Scheme 1), thus indicating the high electrophilicity of isoxazolo[4,3-b]pyridine system. Some of the reactions proceeded almost immediately after mixing the reagents, the others were completed within an hour.…”

“…This work is part of our ongoing research on highly electrophilic systems and the application of the dearomatization strategy in the synthesis of new polyfunctional azaheterocycles [38][39][40][41][42][43][44][45][46][47][48]. We have previously shown that nitropyridines fused with π-deficient heterocycles (furoxan A, selenadiazole B), Scheme 1, react with neutral nucleophiles with the formation of 1,4-addition products-dihydropyridine derivatives [45,46,48]. In addition, these compounds are capable to undergo [4+2]-cycloadditions to the C=C(NO2) aromatic bond, behaving as electron-poor dienophiles with dienes, or as heterodienes with electron-rich dienophiles within normal or inverse electronic demands, respectively [16,[33][34][35].…”

Stable Anionic σ-Complexes of Highly Electrophilic Aromatics and C-Nucleophiles: Synthesis and Oxidation

“…In case of C-nucleophiles these adducts can be isolated. Earlier we reported on reactions of some azolo[b]pyridines with 1,3-dicarbonyl compounds [4][5][6]. In this work we studied the reactions of dinitrobenzoannulated heterocycles (thiadiazole, selenadiazole, pyridine) with anionic C-nucleophiles (mono-and diketones, nitroalkanes and related compounds).…”