Marie-José Pouet

Electrophilic aromatic substitutions: reactions of hydroxy- and methoxy-substituted benzenes with 4,6-dinitrobenzofuroxan: kinetics and mechanism

Rate constants have been determined in aqueous Me2SO mixtures for the reaction of super-electrophilic 4,6-dinitrobenzofuroxan (DNBF) with a series of hydroxy- and methoxy-substituted benzenes whose pKa values range between -3 and -9. The study extends the reactivity range of weakly basic aromatics with DNBF, from the family of indoles previously studied with pKa values ranging from -1 to -6. The overall rate constants for the reactions of DNBF as the electrophile are at least one order of magnitude greater than for the reactions of H3O+ with the same series of aromatics. This lends further credence to the notion that DNBF possesses super-electrophilic properties. An LFER is observed between logk and pK with slope 0.54. In the case of 1,3,5-trimethoxybenzene a significant kinetic isotope effect (KIE) is observed (kH/kD = 3.71 in 50% Me2SO). This system hence affords one of the few instances in which a KIE has been observed in SEAr reactions. It follows from the observed KIE that the addition of DNBF to the aromatic is not rate-limiting and that reversion to reactants and proton loss from the arenonium intermediate occur at comparable rates. Structures of the products of electrophilic substitution have been confirmed by 1H NMR. In all cases the regiochemistry of the reactions was identical to that observed in protonation studies of the starting aromatics.

Interaction of nitroalkane anions with superelectrophilic 4,6-dinitrobenzofuroxan: σ-adduct formation and vicarious heteroaromatic substitution of hydrogen

Carbanions of nitromethane, nitroethane, 1-nitropropane and 2-nitropropane readily add to 4,6-dinitrobenzofuroxan (DNBF) to form carbon-bonded σ-adducts (5a–d) which are very stable and isolable as crystalline alkali salts. In the case of the nitroethane and 1-nitropropane systems, the complexation results in the formation of two chiral centres, so that diastereoisomeric σ-adducts are formed. Structural features are discussed on the basis of the collected 1H and 13C NMR parameters. Contrary to expectation, addition of base (MeO–, CF3CH2O–, NEt3) to dimethyl sulfoxide solutions of 5a–c did not result in further ionization of the nitroalkane moiety and formation of dianions 7a–c. Instead, it promotes a base-catalysed β-elimination of nitrous acid. This process also occurs and is especially clean with the 2-nitropropane adduct 5d, an example of the rare occurrence of a nucleophilic aromatic substitution of an hydrogen atom assisted by the departure of a vicarious nitro group in the exocyclic moiety. The result is re-aromatization of the carbocyclic ring of 5a–d with formation of carbanions (8a–d) which are the conjugate bases of the corresponding 7-R-4,6-dinitrobenzofuroxans (R = Me, Et, Prn, Pri). Despite their lack of stability, NMR characterization of these carbanions could be made. Rate and equilibrium data for DNBF complexation by the four nitroalkane anions studied have been obtained in aqueous solution. The results show that the thermodynamic stability of the adducts 5a–d is 105–108 times greater than that of the analogous σ-adducts of 1,3,5-trinitrobenzene, the common reference aromatic electrophile in σ-complexation processes. Such stability differences emphasize the extremely high electrophilic character of DNBF. Analysis of the rate data reveals that nitrocarbanions exhibit especially low intrinsic reactivities in σ-adduct forming reactions.

Nucleophilic displacement of hydrogen in 4,6-dinitro--benzofuroxan and -benzofupazan. Synthesis of some novel 7-substituted 4,6-dinitro-benzofuroxans and -benzofurazans.

Abstract Formal hydride ion displacement readily occurs in 4,6-dinitro-benzofuroxan and -benzofurazan. This process provides a simple two-step synthesis of some new 7-substituted-4,6 dinitro derivatives.

Electrophilic heteroaromatic substitutions: reactions of 5-X-substituted indoles with 4,6-dinitrobenzofuroxan

The SEAr substitutions of a number of 5-X-substituted indoles (1a–f), 5-X-substituted 2-methylindoles (1g–j) and N-methylindole (1k) by 4,6-dinitrobenzofuroxan (DNBF) have been kinetically studied in 70–30 (v/v) H2O–Me2SO, 50–50 (v/v) H2O–Me2SO, methanol and acetonitrile. The absence of a significant dependence of the rates of reactions on the hydrogen or deuterium labelling at C-3 of the indole ring indicates that electrophilic attack (k1DNBF)by DNBF at this position is the rate-limiting step of the substitutions. However, the k1DNBF rate constants are strongly sensitive to the solvent polarity, the observed reactivity sequence being 70–30 H2O–Me2SO > 50–50 H2O–Me2SO > methanol > acetonitrile. This trend is consistent with a highly dipolar transition state where the development of negative charge in the DNBF moiety is concomitant with that of a partial positive charge on the indole nitrogen. The finding of relatively large negative ρ values (–3.85) for the Hammett plots log k1DNBF=f(σpX)supports this idea. An interesting result is that the effect of the X substituent on the rates (k1DNBF) is the same in the four solvents studied and does not depend upon the substitution at C-2 of the indole ring. However, the Bronsted or Hammett lines for the 5-X-2-methylindoles are located about 1.5 log k unit below those for the 5-X-indoles in a given solvent, showing that the 2-methyl group causes significant steric hindrance to the approach of DNBF from the adjacent C-3 position. Rates of protiodetritiation of a large number of [3-3H]indoles have also been measured in aqueous solution. The data define a unique Bronsted line (βInH= 0.65), implying that the 2-substituents do not exert any steric effect on the rates of the exchange process and suggesting that the correlation can be used to estimate unknown pKa values of indoles with a free 3-position. Comparison of the rates of coupling of indoles with 4,6-dinitrobenzofuroxan with similar data for coupling of these heterocycles with p-nitrobenzenediazonium cation reveals that, despite its neutral character, DNBF is the most electrophilic species. DNBF also appears to be a much stronger electrophile than the proton.

A new feature in the chemistry of nitrobenzofuroxans: ambident reactivity in Diels–Alder condensations

The 4,6-dinitrobenzofuroxan (DNBF) structure is shown to act both as a dienophile and a heterodiene upon treatment with 1-trimethylsilyloxybuta-1,3-diene and vinyl ethyl ether, providing in two steps a highly functionalised stereoselective compound.

NMR characterization of zwitterionic nitrogen-bonded σ-complexes: the imidazole/4,6-dinitrobenzofuroxan system

Abstract Imidazole (ImH) and N-methylimidazole react with 4,6-dinitrobenzofuroxan to form the σ-complexes 1a, H + and 1b,H + . In excess of ImH, 1a,H + is deprotonated to give the anionic σ-complex 1a . 1a,H + and 1b,H + are the first zwitterionic nitrogen-bonded σ-complexes to be firmly characterized by spectroscopy.

Wittig–Horner reagents: structural and conformational study of five- and six-membered cyclic phosphonates and their carbanions. Evidence of anomeric effect in anionic species

A structural and conformational study of the electron-withdrawing substituted phosphonates 2-oxo-1,3,2-dioxaphosphorinanes (1) and (2) and of the related anionic species (3, K+) and (4, K+) in dimethyl sulphoxide has been made. Phosphonates (1) and (2) exist predominantly in the chair form with the PO bond equatorial. The anion (3, K+) gives rise to three rapidly interconverting species, in the chair form, and (4, K+) to two interconverting chairs, chelated to K+. In each anionic species (3) and (4), the PO axially substituted conformer is significantly populated, due to an anomeric effect. The 2-oxo-1,3,2-dioxaphospholane (5) is very sensitive to moisture, and open-chain compounds can be found in solutions of (5), if the solvent is not carefully dried. The related anionic species (6, K+) is not very stable; however, its 1H and 31P n.m.r. data show some similarities with those of the related acyclic compound.

Signs and magnitudes of 1JP–C, 2JP–C, and 3JP–H in some acetylenic PIII and PIV organophosphorus compounds

Coupling constants display a reversal of sign in acetylenic phosphines, 1JP–C 0, 3JP–H < 0; they are positive in acetylenic phosphine oxides and their values suggest dominance by the Fermi contact interaction.

Side-chain electrophilic aromatic substitution in 2-alkyloxa- and 2-alkylthiazolines initiated viaσ-complex formation with super-electrophilic DNBF: a model proinsecticide

A 1H and 13C NMR study of the reaction of a series of 2-alkyloxa- and 2-alkylthiazolines 3-Xa–c with 4,6-dinitrobenzofuroxan (DNBF) in DMSO revealed the formation of the C-bonded σ-adducts 5-Xa–c. Product isolation following addition of Et3N or KOAc, afforded the Et3NH+ or K+ salts of the DNBF adducts, respectively. The NMR results showed conclusively that coupling of the DNBF moiety with the oxazoline or thiazoline heterocycle occurred at the α position of the 2-alkyl side-chain. A most reasonable mechanism for this coupling involves initial formation of a transient N-bonded adduct between the N-heterocycle and DNBF, which subsequently rearranges through the action of base to the C-bonded adduct as the product of thermodynamic control. The relevance of this work to oxa- and thiazoline-based proinsecticide is emphasized.

New octahedral, asymmetric iron carbonyl complexes

Isomerization of the prochiral octahedral complex [FeMe(CO)2(PMe3)2(PMe2Ph)]+[BPh4]–(CO–CO cis, PMe3-PMe3trans) leads exclusively to a new chiral molecule by permutation of PMe2Ph with one of the PMe3 ligands.