4,6-Dinitro-7-methylbenzofuroxan: a strong carbon acid of very low intrinsic reactivity

Terrier, François; Croisat, Denis; Chatrousse, Alain‐Pierre; Pouet, Marie Jose; Hallé, Jean-Claude; Jacob, Guy

doi:10.1021/jo00039a032

Cited by 19 publications

(7 citation statements)

References 4 publications

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“…Owing to the extreme difficulty in achieving the last protonation step of the process, this approach does not work satisfactorily for the nitrobenzoxadiazole series. 14,15 A more general approach is therefore the one dealing with a formal displacement of H Ϫ through chemical oxidation of the σ-complex. 1,[16][17][18][19] While this strategy has † Electronic supplementary information (ESI) available: supplementary Tables S1-S4 (complete 1 H, 19 F and 13 C data).…”

Section: Introductionmentioning

confidence: 99%

σ-Complex formation and oxidative nucleophilic aromatic substitution in 4-nitro-2,1,3-benzoxadiazoles

et al. 2003

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The feasibility of carrying out nucleophilic displacement of hydrogen from highly electron-deficient heteroaromatics has been addressed through a detailed investigation of the interaction of a series of nitrobenzofuroxans 3a-i and two related heterocycles 5 and 6, with the 2-nitropropenide anion. Although this series corresponds to a large modulation in the electrophilic properties of the six-membered ring, all reactions first lead to the quantitative formation of the sigma-adducts C-3a-i, C-5 and C-6 arising from covalent addition of the nucleophile to the C-7 carbon. With the exception of the 4-aza substituted member C-5, all the adducts have been isolated as pure and very stable alkali salts. Measurements of the oxidation potentials by cyclic voltammetry reveal that the ease of subsequent hydrogen substitution at carbon-7 strongly decreases with increasing electron deficient character of the six-membered ring. The measured E0 values are in the range 0.5-0.6 V (vs. SCE) for the 4-nitro-benzofuroxan and -benzofurazan adducts (C-3e, C-3i) but they go up to 1.20-1.33 V for the 4,6-dinitro- and 4-nitro-6-trifluoromethanesulfonylbenzofuroxan adducts (C-3a,d) in acetonitrile. Consistently with these E0 values, only very powerful oxidants such as the Ce4+/Ce3+ or the MnO4-/Mn2+ couples can successfully oxidize the adducts leading to the expected substitution products in moderate to good yields (35-72%). Interestingly, the rearomatization of the 4-nitro substituted benzofuroxan adducts proceeds with a partial Boulton-Katritzky rearrangement of the resulting products. Another noteworthy result is that the 4-nitrobenzofuroxan and 4-nitrobenzofurazan molecules suffer competitive addition of the (CH3)2C-NO2- anion to the 5- and 7- positions under some experimental conditions. This represents the first well-defined example of isomeric addition of a carbon nucleophile to these heterocycles.

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Section: Introductionmentioning

confidence: 99%

σ-Complex formation and oxidative nucleophilic aromatic substitution in 4-nitro-2,1,3-benzoxadiazoles

et al. 2003

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“…The action of the methoxide anion on the 4,6-dinitro7-methylbenzofuroxan (DNBF) leads only to the isolation of the anionic form DNBF -. The anion DNBF - [23,24] has a pKa of 2.5, a value very close to those of mineral acids. It is one of the best superelectrophiles on the scale established by Mayr.…”

Section: Introductionmentioning

confidence: 85%

Theoretical investigation of methoxide ion reaction on the 7-methyl-4,6-dinitrobenzofuroxan

2016

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Reaction of the methoxide ion on the 7-methyl 4,6-dinitrobenzofuroxan (DNBF) 1 has been studied theoretically by means of DFT/B3LYP technique in order to interpret the kineticthermodynamic competition between the three possible compounds that are carbanion DNBF -4 and two complexed forms (2, 3) of the methoxide group in positions 5 and 7 respectively. Optimized Geometry, nbo atomic charge distribution, thermodynamic/kinetic parameters (∆ r H°T, ∆ r S°T , ∆ r G°T, ∆H*, ∆S* and ∆G*) and IRC path have been calculated for possible products and their transitional states using water as solvent. All obtained ∆ r G°T are negative, ranging from -19.16 to -42.87 kcal mol -1 , indicating the possible observation of all products but the experimenters only detected the anionic form DNBF -. Fukui indices, which were calculated by means of NBO atomic charge distribution, confirm the electrophilicity of the sites C5 and C7. Transition states barriers, ΔG* are 14.97 , 15.16 and 21.94 kcal mol -1 for the three possible products 2, 3 and 4 respectively in water. As expected, the most stable compound is the carbanion but it exhibits also the highest activation barrier. If this situation engenders formally a double kinetic-thermodynamic competition, the very weak activation energy of the two complexes in C5 and C7 makes improbable the simultaneous detection of the three expected compounds.

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“…1,2,5-benzoxadiazols and their N-oxides were synthesized using the conventional [ 20 – 22 ] or analogous procedures.…”

Section: Methodsmentioning

confidence: 99%

Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors

et al. 2013

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Human immunodeficiency virus type 1 integrase is one of the most attractive targets for the development of anti-HIV-1 inhibitors. The capacity of a series of 2,1,3-benzoxadiazoles (benzofurazans) and their N-oxides (benzofuroxans) selected using the PASS software to inhibit the catalytic activity of HIV-1 integrase was studied in the present work. Only the nitro-derivatives of these compounds were found to display inhibitory activity. The study of the mechanism of inhibition by nitro-benzofurazans/benzofuroxans showed that they impede the substrate DNA binding at the integrase active site. These inhibitors were also active against integrase mutants resistant to raltegravir, which is the first HIV-1 integrase inhibitor approved for clinical use. The comparison of computer-aided estimations of the pharmacodynamic and pharmacokinetic properties of the compounds studied and raltegravir led us to conclude that these compounds show promise and need to be further studied as potential HIV-1 integrase inhibitors.

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4,6-Dinitro-7-methylbenzofuroxan: a strong carbon acid of very low intrinsic reactivity

Cited by 19 publications

References 4 publications

σ-Complex formation and oxidative nucleophilic aromatic substitution in 4-nitro-2,1,3-benzoxadiazoles

σ-Complex formation and oxidative nucleophilic aromatic substitution in 4-nitro-2,1,3-benzoxadiazoles

Theoretical investigation of methoxide ion reaction on the 7-methyl-4,6-dinitrobenzofuroxan

Structural-Functional Analysis of 2,1,3-Benzoxadiazoles and Their N-oxides As HIV-1 Integrase Inhibitors

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