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

Abstract

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.

The ambident electrophilic behavior of 5‐nitro‐3‐X‐thiophenes in σ‐complexation processes

“…Previous papers that have been already published in this field also reveal concurrent addition at unsubstituted positions in many heterocyclic systems . Terrier and co‐workers, for example, have demonstrated that the reaction of 3,5‐dinitropyridine 9 with the methoxide ion in methanol occurs more rapidly at the C‐4 position (σ‐adduct 10 ) than at the C‐2 position ,favoring the formation of the thermodynamically more stable isomer 11 …”

“…This suggests that isomeric addition of phenoxide anions to Previous papers that have been already published in this field also reveal concurrent addition at unsubstituted positions in many heterocyclic systems. [24][25][26][27][28] Terrier and co-workers, for example, have demonstrated that the reaction of 3,5dinitropyridine 9 with the methoxide ion in methanol occurs more rapidly at the C-4 position ( -adduct 10) than at the C-2 position ,favoring the formation of the thermodynamically more stable isomer 11. 25 Kinetic measurements of the reactions of thiophenes 1 and 2 with the reference parasubstituted phenoxide anions 3ad were performed spectrophotometrically at or close to the absorption maxima of the -adducts 5-8 in aqueous solution at 20 • C under pseudo-first-order conditions in which the nucleophile concentration was kept in excess of the electrophiles.…”

Electrophilicities of 4‐Nitrobenzochalcogenadiazoles

“…[19,23,25,41,42] Another interesting result is the finding that nitrobenzoselenadiazole 1 b is 2 orders of magnitude more electrophilic than 1,3,5-trinitrobenzene 8 (E =-13.19), [35] the common reference aromatic electrophile in σ-complexation processes. [18][19][20][21][22][23][24]…”

“…(1) usually predicts rate constants of polar organic reactions within a factor of 10-100. [16,21,35,[44][45][46][47][48][49][50][51][52][53][54] Follet and co-workers [46] have shown that Eq. (1) predicts the rate constants for reactions of indol-3-ylmethylium ions with various phosphines and pyridines in dichloromethane solutions at 20°C within a factor of 0.33-87.2.…”

“…[15] In earlier work we have shown that 4-nitrobenzofurazan 1 c [16] is a representative of an another class of neutral electro-philes whose C-electrophilicity can be quantitatively described by the linear free enthalpy relationship (1), [17] where E parameter measures the strength of the electrophile, k is a second-order rate constant, while N and s N characterize the nucleophiles reactivity. log k ð20 � CÞ ¼ s N ðE þ NÞ (1) In an effort to obtain a quantitative measure of the reactivity of nitro derivatives of 2,1,3-benzothiadiazole and 2,1,3-benzoselenadiazole towards nucleophilic addition processes, [18][19][20][21][22][23][24] we now report on the kinetic and structural analysis of the coupling reaction of 4-nitrobenzothiadiazole 1 a and 4-nitrobenzoselenadiazole 1 b with the reference nitroalkyl anions 2 a-c (Scheme 1, Table 1) in order to evaluate the electrophilic parameter E at the C-7 position of the two electrophiles 1 a and 1 b according to Eq. (1) and to include them into the comprehensive electrophilicity scale of Mayr.…”