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International audience; (Z)- and (E)-iminoacetonitriles (NCCH═NH), two hydrogen cyanide dimers, are described as key compounds in prebiotic chemistry. Among the many possible dimers of HCN with covalent bonds, even the second on the scale of thermodynamic stability, methylenecyanamide (CH(2)═NCN), has been investigated little. We show that this compound can be isolated, is stable enough to give an adduct with a nucleophile or a diene, and can be easily generated under prebiotic conditions, highlighting a possible role in this medium. Comparison between isomers shows significant differences in formation and chemical reactivity.

A facile synthetic method for N-alkylated substituted benzochalcogenadiazoles is described. When treated with Meerwein salt, the 4-nitrobenzochalcogenadiazoles have undergone an N-alkylation to afford the expected salts as a mixture of two N1/N3 isomers in toluene. The regioselectivity of the alkylation reaction was then confirmed by spectroscopic data as well as theoretical calculations.

Nonlinear optical (NLO) effects of organic materials are caused by delocalized electrons and large polarization in molecules. In the present work, theoretical study by using the Density Functional Theory (DFT) at B3LYP/6-311G(d,p) level of theory on three types of pyridine derivates 2,6-dimethoxy-3,5-dinitropyridine (M1), 2-methoxy-3-nitropyridine (M2) and 2-methoxy-5-nitropyridine (M3) is reported. The nuclear magnetic resonance (1H and 13C NMR) chemical shifts of the title compounds were calculated using the Gauge Independent Atomic Orbital (GIAO) method and compared to the observed results. Both infrared absorption and Raman are complementary to provide characteristic fundamental vibrations that are necessary for the identification of the molecular structures. Electronic properties such as frontier molecular orbital (HOMO, LUMO), ionization potential ( IP ad ) and electronic affinity ( EA ad ) were determined to get better insight into the molecular properties. Using the Time-Dependent Density Functional Theory (TD-DFT), electronic absorption spectra have been predicted and closely matching the experimental findings. The natural bonding orbital (NBO) calculations were performed in order to elucidate various second order interactions in between the filled and vacant orbitals which are a measure of the intermolecular as well as the delocalization within the molecule. In addition, we have demonstrated that these molecular systems have large first static hyperpolarizabilities and may have potential applications in the development of NLO materials.

The carbon-carbon cross-coupling of phenyl s-tetrazine (Tz) units at their ortho-phenyl positions allows the formation of constrained bis(tetrazines) with original tweezer structures. In these compounds, the face-to-face positioning of the central tetrazine cores is reinforced by π-stacking of the electron-poor nitrogen-containing heteroaromatic moieties. The resulting tetra-aromatic structure can be used as a weak coordinating ligand with cationic silver. This coordination generates a set of bis(tetrazine)-silver(I) coordination complexes tolerating a large variety of counter anions of various geometries, namely, PF6−, BF4−, SbF6−, ClO4−, NTf2−, and OTf−. These compounds were characterized in the solid state by single-crystal X-ray diffraction (XRD) and diffuse reflectance spectroscopy, and in solution by 1H-NMR, mass spectrometry, electroanalysis, and UV-visible absorption spectrophotometry. The X-ray crystal structure of complexes {[Ag(3)][PF6]}∞ (4) and {[Ag(3)][SbF6]}∞ (6), where 3 is 3,3′-[(1,1′-biphenyl)-2,2′-diyl]-6,6′-bis(phenyl)-1,2,4,5-tetrazine, revealed the formation of 1D polymeric chains, characterized by an evolution to a large opening of the original tweezer and a coordination of silver(I) via two chelating nitrogen atom and some C=C π-interactions. Electrochemical and UV spectroscopic properties of the original tweezer and of the corresponding silver complexes are reported and compared. 1H-NMR titrations with AgNTf2 allowed the determination of the stoichiometry and apparent stability of two solution species, namely [Ag(3)]+ and [Ag(3)2]2+, that formed in CDCl3/CD3OD 2:1 v/v mixtures.

σ-complexation reactions of 2-N-(4′-X-pheny1)-4,6-dinitrobenzotriazole 1-oxides 1a (X = CH3) and 1e (X = CF3) with a series of C-nucleophiles, as reference, have been investigated kinetically in aqueous solution at 20 °C. The reactions are second-order and exhibit electrophilicity parameter E = -10.25 for 1a and E = -11.66 for 1e. Comparison with other derivative benzotriazoles 1a, 1c, 1d, and 1f–i reported in preceding papers is discussed, and it is shown that the E vs. pKa plot is nonlinear. In this context, geometries optimization of electrophiles 1a–i were performed at density functional theory (DFT) with the B3LYP hybrid functional and the 6–31 g(d,p) and 6–31 + g(d,p) basis sets, in acetonitrile, using the Gaussian 09 package, in order to clarify the negative deviations observed for benzotriazoles 1h and 1i. Thus, the origin of the nonlinear E vs. pKa plot was interpreted in terms of strong steric compression of the adjacent ortho-nitro and N-oxide functions. In addition, Parr's electrophilicity indices ω for these series of benzotriazoles 1a–i were calculated from the electronic chemical potential μ and the chemical hardness η and compared to experimental electrophilicity parameters E. More importantly, it has been shown that such theoretical and experimental electrophilicity scales are linearly and directly related to the correlation parameters of r2 > 0.97.

Kinetics of the nucleophilic aromatic substitution reactions of 7-L-4-nitrobenzofurazans 1 (1a: L = Cl and 1b: L = OCH3) and secondary cyclic amines (morpholine, piperidine, and pyrolidine) 2a–c have been measured in acetonitrile solution at 20°C. The derived values of second-order rate constants (k1) have been employed to determine the electrophilicity parameters E for both benzofurazans 1a and 1b according to the linear free enthalpy relationship: log k (20°C) = sN(E + N) (Eq. (1)). The second-order rate constants for reactions of benzofurazans 1 with a series of 4-X-substituted anilines 3a–d (X = OH, OCH3, CH3, and H) have also been measured in MeCN and found to agree within a factor of 0.14–50 with those calculated by Eq. (1) from the electrophilicity parameters E measured in this work and the known nucleophile-specific parameters N and sN of anilines 3. On the other hand, the reactions of these benzofurazans 1 with anilines 3 exhibit linear Bronsted-type plots with βnuc = 1.27 for 1a and 1.01 for 1b, which are considerably greater than those (0.57 for 1a and 0.62 for 1b) obtained with the secondary cyclic amines 2. These high values of βnuc have been interpreted in terms of a single electron transfer mechanism. Secondary evidence for the validity of this mechanism is provided by the agreement between the rate constants, k1, for substitution of benzofurazans 1 by the anilines 3 and their oxidation potentials E°.

The kinetics of the reactions of benzylidenecyanoacetates 1a–d (X = H, Me, OMe, and NMe2) with nitroalkyl anions 2a–c have been studied in aqueous solution at 20°C. The second-order rate constants are used to evaluate the electrophilicity parameter E of these series of Michael acceptors 1a–d according to the linear free enthalpy relationship log k (20°C) = sN (E + N). The measured E values were found to cover a domain of reactivity, ranging from −10.07 for the most reactive electrophile 1a (X = H) to −14.04 for the less electrophile 1d (X = NMe2). Mayr's approach was found to correctly predict the rate constants for the reactions of these series of olefins 1a–d with the hydroxide ion in water and 50% water–50% acetonitrile at 20°C. Analysis of the kinetic measurements using the Bronsted relationship shows that βnuc values remain remarkably constant for changes in the nature of the substituent X. A notable finding of this work is perhaps provided by the observed large changes in the electrophilicity parameter E on going from benzylidenecyanoacetates 1 to their analogues benzylidenemalonates 3 (ΔE ∼ 9.06–10.48), whereas the replacement of second CO2Et group by the CN group in 1 to give benzylidenemalononitriles 4 has little effect on electrophilic reactivity, i.e., ΔE ∼ 0.65–0.95. This abnormal pattern in the E values has been attributed to the resonance interaction and salvation effects. On the other hand, the effect of benzylidenecyanoacetate substituents on the electrophilic reactivity was examined quantitatively on the basis of the electrophilicity parameter E, leading to linear correlation of E with Hammett–Brown substituent constants (σp+). More importantly, the four electrophiles have comparable log ko values, which are located at a relatively low level, i.e., log ko ≤ 4–5, in the intrinsic reactivity scale.

Second-order rate constants (k1) for the σ-complexation of 4-nitrobenzofurazan 1 with four 4-X-substituted phenoxide anions 2a–2d (X = OCH3, CH3, H and Cl) were measured in aqueous solution at 20 °C. Using this series of phenoxide anions as a reference, the electrophilicity parameter (E) of this electrophile 1 has been evaluated according to Mayr’s approach. With the E value of –9.42, Mayr’s equation was found to correctly predict the rate constants for the reactions of 1 with hydroxide ion in H2O and a 1:1 ratio of H2O to CH3CN. However, the large βnuc value of 1.12 obtained in the present work is clearly consistent with a single electron transfer (SET) mechanism.

The nucleophilic addition reactions of N1-methyl-4-nitro-2,1,3-benzoselenadiazolium tetrafluoroborate 1 with aliphatic amines 2a–c (diethylamine 2a, dipropylamine 2b, and allylamine 2c) have been kinetically studied by UV–vis spectroscopy in acetonitrile solution at 20°C. The kinetic data have been analyzed, using the Mayr equation, allowing the quantification of the electrophilicity parameter (E) value of benzoselenadiazolium cation 1 (E = −14.72). The reliability of parameter E has been reasonably verified by comparison of calculated and experimental second-order rate constants for the reactions of cation 1 with other amines 2d–f (pyrrolidine 2d, piperidine 2e, and morpholine 2f) under the same conditions as those of the amines 2a–c. A linear Bronsted plot (R2 = 0.9945) with a βnuc value of 0.55 has been obtained for the reactions of 1 with the secondary amines employed in the present work. Interestingly, satisfactory correlation between the log values of measured and calculated rate constants with a slope very close to unity has been obtained and discussed.

Metal-catalysed ortho-directed C–H functionalization usually faces selectivity issues in the competition between mono- and disubstitution processes. We report herein the ruthenium-catalysed N-directed C–H monoarylation of arylpyrazoles with a selectivity of up to 96% or that generally reaches values above 80%. This selectivity is an effect of solvent-free conditions associated with sulfonate reagents, in the absence of frequently used acidic additives.

Kinetics of the reactions of 7-Imidazolium-4-nitrobenzofurazan 1a and 7-phenoxy-4-nitrobenzofurazan 1b with secondary amines 2a-c were studied spectrophotometrically in acetonitrile at 20 °C. The second-order rate constants have been used to evaluate the electrophilicity parameters E of 1a and 1b according to the linear free energy relationship log k (20 °C) = s (N + E). The theoretical electrophilic reactivity of the 7-phenoxy-4-nitrobenzofurazan 1a and 7-Imidazolium-4-nitrobenzofurazan 1b and two other nitrobenzofurazans 1c (L = OCH3) and 1d (L = Cl) have been studied by Density Functional Theory (DFT/B3LYP: Becke, 3-parameter, Lee- Yang-Parr) and the 6–311g(d,p) basis set implemented in Gaussian 09W Software. The derived electronic chemical potential (μ) and the corresponding chemical hardness (η) parameters have been used to calculate the global electrophilicity index (ω) of these series of electrophiles defined by the relationship ω = μ2/η. A good correlation between the calculated ω values and their experimentally observed electrophilic reactivities (i.e., Mayr’s electrophilicities E) is found and discussed.

International audience

The kinetics of the coupling of N1-methyl-4-nitro-2,1,3 benzothiadiazolium tetrafluoroborate 1 with a series of 4-X-substituted anilines 2a–f (X = OH, OMe, Me, H, Cl, and CN) have been investigated in acetonitrile at 20°C. The second-order rate constants result in a nonlinear Bronsted-type plot. The Hammett plot is also nonlinear, whereas the Yukawa–Tsuno plot exhibits an excellent linear correlation with ρ = –1.62 and r = 1.44. The large Bronsted (βnuc = 1.24) and Hammett (ρ = –5.16) values suggest that the reactions proceed trough a single electron transfer mechanism. The finding of satisfactory correlation between the log k1 of the reactions and the oxidation potentials (E°) of anilines 2a–d supports this mechanism. On the other hand, electrophilicity parameter E of benzothiadiazolium cation 1 as defined by the correlation log k20°C = s(E + N) has been determined and compared with the electrophilic reactivities of a large variety of electrophiles.

Second-order rate constants for the reactions of 2-aryl-4,6-dinitrobenzotriazole 1-oxides 1a-d with some 4-X-substituted phenoxide ions 2a-d (X = OCH3, H, Cl, and CN) have been measured in aqueous solution at 20°C. The pKa values for the σ-complexation processes of a series of benzotriazole 1a-d measured in water have been used to determine their electrophilicity parameters E according to the correlation E = –3.20 – 0.662 pKa (F. Terrier, S. Lakhdar, T. Boubaker, and R. Goumont, J Org Chem, 2005, 70, 6242–6253). For these reactions, plots of log k versus the electrophilicity parameters E of the benzotriazoles 1a-d were linear, allowing to derive the nucleophilicity parameters N and s for phenoxide ions as defined by the Mayr equation log k1 (20°C) = s (E + N) (H. Mayr, M. Patz. Angew Chem, Int Ed Engl 1994, 33, 938–957). The N values are found to cover a range of nucleophilicity from 6.85 to 10.22, going from 4-cyanophenoxide 2d for the least reactive ion to 4-methoxyphenoxide 2a for the most reactive nucleophile. Good linear correlations were found between the nucleophilicity parameters N of phenoxide ions 2a-d and the pKa values of their conjugate acids (N = –3.05 + 1.25 pKa) and the constants of the substituents X (N = 9.21 – 2.51).

The kinetics of σ complexation of unsymmetrical 2-nitro-4,6-bis(trifluoromethylsulfonyl)anisole (1e) has been investigated over a large pH range of 2.7–15.68 in methanol. Two competitive σ complexation processes have been identified that lead, respectively, to the formation of the 1,3- and 1,1-adducts 2e and 3e of 1e. No evidence for nucleophilic addition at the unsubstituted 5-position para to the nitro group of 1e to afford the 1,5-dimethoxy adduct 4e could be obtained. The observed regioselectivity supports the view derived from previous investigations that a SO2CF3 group exerts a much stronger electron-withdrawing effect than a NO2 group, both in the ortho and para positions of a reactive centre in an aromatic ring. In accord with this conclusion, the 1,1-dimethoxy adduct 3e is found to be 102-fold less stable than the tris-SO2CF3 analogue 3a but ten times more stable than the 1,1-dimethoxy adduct 3b of 4-nitro-2,6-bis(trifluoromethylsulfonyl)anisole (1b). However, a most significant result is the finding that the solvent contribution to the formation of 3e is not negligible in the pH range of 9–10. With a pKaMeOH value of 9.42, the electrophilic reactivity of the parent triflone 1e is clearly located in the region of extremely high electrophilicity defined for σ complexation and SNAr substitutions in methanol (pKaMeOH ≤ 9–10). This work adds to the recognition that the activating effect of a SO2CF3 group is in general much greater than that of a NO2 group when bonded to an aromatic or heteroaromatic ring. A return to the origin of the exceptional electron-transmission capability of the SO2CF3 group is helpful to predict reactivity.

A kinetic study is reported for reactions of 2-methoxy-3-X-5-nitrothiophenes 1a–d (X = SO2CH3, CO2CH3, CONH2, H) with piperidine in different solvents at 20°C. It is shown that the reactions take place through a SNAr mechanism with the initial nucleophilic addition step being rate limiting. The satisfactory Hammett correlations (log k1 vs. σ) obtained in the present system confirms that a 3-X substituent exerts an effect on the 2-position of the same type as that exerted from the 5-position. The second-order rate constants associated with these reactions are employed to determine the electrophilicity parameters E of the thiophenes 1a–d according to the relationship log k (20°C) = s(E + N) (Angew. Chem., Int. Ed. Engl. 1994, 33, 938–957). The E values of 1a–d are found to cover a range from −21.33 to −17.18, going from 1d, the least reactive, to 1a, the most reactive thiophene. Interestingly, a linear correlation (r2 = 0.9910) between the electrophilicity parameters E determined in this work and the Hammett's σ constants values has been observed and discussed. On the other hand, we have found that the reported rate constants of some thiophenes 1 complexation by the methoxide ion in methanol are 3.5–73.5 times higher than predicted by Mayr's approach.

Kinetic studies for the Michael-type reactions of ethyl-3-(4′-N,N-dimethylaminophenyl)-2-(nonafluorobutane)sulfonylpro-penoate 1 with 4-X-substituted anilines 2a–e (X = OCH3, CH3, H, F, and Cl) have been investigated in acetonitrile at 20°C. A quadratic dependence of the pseudo–first-order rate constants (kobsd) versus [2a–e] has been observed and has been interpreted in terms of a dimer nucleophile mechanism. The finding of a relatively large negative ρ value (−3.09) for the Hammett plot suggests that the intermediate (I±) is highly zwitterionic in nature. A linear correlation (r2 = 0.9989) between the Hammett's substituent constants σ and nucleophilicity parameters N of 4-X-substituted anilines in acetonitrile has been observed. The electrophilicity parameters E of the olefin 1 is evaluated, using the correlations σ versus N and log k versus σ and compared with the electrophilicities of analogously Michael acceptors.

A modular indole synthesis based on an intramolecular 5-endo-dig carbocupration starting from readily available N-aryl-ynamides is reported. A variety of ynamides are converted to indoles in moderate to good yields and with varying substitution pattern on the indole ring. This further extends the synthetic utility of ynamides in organic synthesis and provides additional insights on the use of intramolecular carbometalation reactions.

The kinetics and mechanism of nucleophilic aromatic substitution reactions of 4-chloro-7-nitrobenzofurazan 1 with 4-X-substituted anilines 2a–g (X = OH, OCH3, CH3, H, I, Cl, and CN) are investigated in a dimethyl sulfoxide (Me2SO) solution at 25°C. The Hammett plot of log k1 versus σ is nonlinear for all the anilines studied due to positive deviations of the electron-donating substituents. However, the corresponding Yukawa–Tsuno plot resulted in a good linear correlation with σ+r (σ+−σ). The corresponding Bronsted-type plot is also nonlinear, i.e., the slope (βnuc) changes from 1.60 to 0.56 as the basicity of anilines decreases. These results indicate a change in a mechanism from a polar SNAr process for less basic nucleophiles (X = I, Cl, and CN) to a single electron transfer for more basic nucleophiles (X = OH, OCH3, and CH3). The satisfactory log k1 versus Eo correlation obtained for the reactions of 1 with anilines 2a–d in the present system is consistent with the proposed mechanism. Interestingly, the βnuc = 1.60 value measured for 1 in Me2SO reflects one of the highest coefficients Bronsted ever observed for SNAr reactions. © 2013 Wiley Periodicals, Inc. Int J Chem Kinet 45: 152–160, 2013

A kinetic study is reported for SNAr reactions of 2,4,6-tris(trifluoromethanesulfonyl) anisole 1a with a series of para-X-substituted anilines 2a–e in a methanol solution at various temperatures. The substituent effects on free energy (Δ≠G), enthalpy (Δ≠H), and entropy (Δ≠S) of activation are examined. Aniline addition to triflone 1a is characterized by a βX=0.57, αZ=0.31, and an imbalance of I = αZ–βX=−0.26. The imbalance shows that resonance development lags behind CN bond formation at the transition state. Interestingly, analysis of the results in terms of Marcus theory reveals that these SNAr are associated with some extremely low intrinsic reactivity (log ko=−1.25& © 2011 Wiley Peiodicals, Inc. Int J Chem Kinet 43: 255–262, 2011

The rate constants for the reaction of 2,6-bis(trifluoromethanesulfonyl)-4-nitroanisole with some substituted anilines have been measured by spectrophotometric methods in methanol at various temperatures. The data are consistent with the SNAr mechanism. The effect of substituents on the rate of reaction has been examined. Good linear relationships were obtained from the plots of log k1 against Hammett σpara constants values at all temperature with negative ρ values (−1.68 to −1.11). Activation parameters Δ≠H varied from 41.6 to 54.3 kJ mol−1 and Δ≠S from −142.7 to −114.6 J mol−1 K−1. The δΔ≠H and δΔ≠S reaction constants were determined from the dependence of Δ≠H and Δ≠S activation parameters on the σ substituent constants, by analogy with the Hammett equation. A plot of Δ≠H versus Δ≠S for the reaction gave good straight line with 177°C isokinetic temperature. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 203–210, 2010

The kinetics of sigma complexation of 2,4,6-tris(trifluoromethanesulfonyl)anisole (7 d) have been investigated over a large pH range of 2-13.70 at T = 20 degrees C in methanol. Two competitive processes associated with the initial addition of MeO(-) at the unsubstituted 3-position of 7 d to give a 1,3-dimethoxy adduct (9 d-Me) and a subsequent and slow conversion of this species into a 1,1-dimethoxy isomer (8 d-Me) have been identified. Both adducts 8 d-Me and 9 d-Me are 10(5)-10(6) times more stable than the related adducts 8 a-Me and 9 a-Me of 2,4,6-trinitroanisole (7 a), a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high stability of 8 d-Me and 9 d-Me is shown to derive from greater rates of formation and lower rates of decomposition than previously determined for 8 a-Me and 9 a-Me, thereby emphasising the especially high activation of a benzene ring by SO(2)CF(3) group(s). Analysis of the collected rate and equilibrium data for sigma complexation in the anisole series 2,4,6-tris(SO(2)CF(3))-, 2,6-bis(SO(2)CF(3))-4-nitro-, 4-SO(2)CF(3)-2,6-dinitro- and 2,4,6-trinitro- supports the idea that the especially high capacity of resonance stabilisation of the negative charge of the adducts through an F(pi)-type (as defined in ref. 49) polarisation effect is a major factor that accounts for the strong activation provided by SO(2)CF(3) groups. A most significant result is the finding that the 1,1-dimethoxy adduct 8 d-Me is by far the most stable benzene sigma adduct so far reported. With a pK(a)(MeOH) value of 7.32, this adduct is formed exclusively through methanol addition up to pH approximately 10. This is consistent with the location of 7 d in the superelectrophilic region defined by pK(a)(MeOH) < or = 9.5-10.5. For comparison, the solvent contribution is negligible in the formation of the 1,3-isomer 9 d-Me, the pK(a)(MeOH) (10.59) of which is situated on the upper limit of the boundary. Taking advantage of the simple relationship linking pK(a) values for sigma complexation in methanol and water, a ranking of the triflone 7 d on the general thermodynamic scale constructed for Meisenheimer electrophiles in water is informative. An approximate calibration on the electrophilicity scale kinetically derived by Mayr et al. has also been made.

We report on the dual reactivity, i.e. anionic Meisenheimer sigma adduct formation and Diels-Alder adduct formation, of a series of heteroaromatic super-electrophiles, including 4,6-dinitro-benzofuroxan, -N-arylbenzotriazoles (4), -benzothiadiazole and -benzoselenadiazole. Measured pK(a)(H(2)O) values for sigma adduct formation provide a quantitative measure of super-electrophilic reactivity with a satisfactory correlation between the Mayr E electrophilicity parameter and pK(a)(H(2)O): E = -0.662 pK(a)(H(2)O) (or pK(R+) -3.20 (r(2) = 0.987). The most highly electrophilic, pre-eminent super-electrophile is 4,6-dinitrotetrazolopyridine (E = -4.67, pK(a)(H(2)O) = 0.4), which supercedes the reference Meisenheimer super-electrophile, 4,6-dinitrobenzofuroxan (E = -5.06, pK(a) = 3.75), having itself an E value superior by 8 orders of magnitude compared to 1,3,5-trinitrobenzene as the benchmark normal Meisenheimer electrophile (E = -13.19, pK(a)(H(2)O) = 13.43). (For relevant kinetic parameters as well as E and pK(a) values, see .) In a parallel study we have investigated Diels-Alder (normal and inverse electron demand) reactivity of this series of heteroaromatic electrophiles and have shown that Mayr E values are valid predictors of whether DA adducts will form and how rapidly. The observed order of pericyclic reactivity corresponds to E = -8.5 as the demarcation E value, in close agreement with sigma complexation; thus pointing to a common origin for the two processes, i.e. an inverse relationship between the degree of aromaticity of the carbocyclic ring and ease of sigma complexation, or DA reactivity, respectively.

The kinetics of the reactions of a series of reference carbon nucleophiles, consisting of N-methylpyrrole A, indole B, N-methylindole C, and enamines D-G, with 10 electron-deficient aromatic and heteroaromatic substrates (1-10), resulting in the formation of stable anionic sigma-adducts, have been investigated in acetonitrile at 20 degrees C. It is shown that the second-order rate constants k(1) pertaining to the carbon-carbon coupling step of these processes fit nicely the three-parameter equation log k (20 degrees C) = s(N + E), allowing the determination of the electrophilicity parameters E of 1-10 and therefore the ranking of these neutral electron-deficient compounds on the comprehensive electrophilicity scale defined for cationic electrophiles by Mayr et al. (Mayr, H.; Kempf, B,; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66). The E values of 1-10 are found to cover a range from -13 to -5, going from 1,3,5-trinitrobenzene 1, the least reactive molecule, to 4,6-dinitrotetrazolo[1,5-a]pyridine 8, 4-nitro-6-trifluoromethanesulfonylbenzofuroxan 3, and 4,6-dinitrobenzofuroxan 2, the three most reactive heterocycles. Of major interest is that the E value of 2 is essentially the same as that for 4-nitrobenzenediazonium cation (E = -5.1), approaching that of the tropylium cation family (E approximately -3 to -6) as well as a number of metal-coordinated carbenium ions. Such a ranking holds promise for expanding the range of coupling reactions which can be envisioned with such strongly electron-deficient neutral heteroaromatics as nitrobenzofuroxans and related compounds. Arguments are also given which exclude the possibility for the reactions studied to proceed via an electron-transfer mechanism.

As part of our continuing studies of the highly electron-deficient nature of nitrobenzofuroxans, nitrobenzofurazans and related heterocycles, we report here a kinetic and thermodynamic study of σ-complexation for a series of 2-aryl-4,6 -dinitrobenzotriazole 1-oxides (3a–e) over a large pH range in aqueous solution. The reaction series represents a modulation in electrophilic properties of the benzotriazole moiety in formation of the corresponding hydroxy σ-adducts (4a–e). Analysis of the data has allowed dissection of observed rates into forward (kH2O1, kOH−2) and reverse (kH+−1, k−2) rate constants as well as the obtention of pKa values for H2O addition to the benzotriazole moiety. Our results reveal that 3a–e are superelectrophilic compounds with respect to 1,3,5-trinitrobenzene (TNB) as a standard electron-deficient aromatic, but less superelectrophilic compared to 4,6-dinitrobenzofuroxan (DNBF). Some data pertaining to buffer catalysis of the formation and decomposition of the adducts together with solvent deuterium isotope effects for these pathways are also reported. From these results, it is concluded that adduct formation occurs via general base catalyzed water attack: the general bases include notably H2O, HCO3−, CO32− as well as OH−. This contrasts with the situation for the σ-complexation of DNBF where HCO3− and CO32− were found to act as nucleophilic catalysts whereas OH− functioned as a general base catalyst. This contrasting behaviour provides further evidence that the dinitro-activated carbocyclic ring of the benzotriazoles 3a–e ranks somewhat lower in electrophilic/superelectrophilic properties compared to that in DNBF. Altogether, the results provide a basis for understanding the relationship between the superelectrophilic reactivities, as evidenced by the contrasting kinetic and thermodynamic properties of the systems at hand, and the varied abilities of these substrates to react in pericyclic Diels–Alder reactions.

Insights into the reactivity of ynimines under anionic conditions are reported. They were shown to be excellent precursors of metalated ketenimines, which can be generated in situ by the reaction of ynimines with organolithium reagents or strong bases. The metalated ketenimines can then be trapped with various electrophiles and, depending on their substitution pattern, afford original and divergent entries to various building blocks.

A two-pronged study of a series of 2-aryl-4,6-dinitrobenzotriazole 1-oxide substrates (2a–c) is reported: Diels–Alder type pericyclic reactivity and covalent hydration to yield Meisenheimer type hydroxy anionic σ-adducts. The most activated benzotriazole 1-oxide 2a is found to exhibit both dienophilic and heterodienic behaviour on treatment with cyclopentadiene, providing a highly functionalized stereoselective diadduct (7). This diadduct is shown to be the result of two consecutive inverse demand Diels–Alder condensations proceeding through the endo mode with a trans addition of two cyclopentadiene molecules. Kinetic and thermodynamic measurements of the ease of covalent hydration of 2a–c to give σ-adducts 4a–c in aqueous solution indicate that the electrophilic reactivity of the 4,6-dinitrobenzotriazole 1-oxide structure is much closer to that of the superelectrophilic 4,6-dinitrobenzofuroxan (DNBF, 1a) than that of the standard Meisenheimer electrophile 1,3,5-trinitrobenzene (TNB). The pKa values range from 6.70 for the 2-(2',4',6'-trinitrophenyl)-4,6-dinitrobenzotriazole 1-oxide (Pi-DNBT, 2a) to 10.73 for the 2-phenyl-4,6-dinitrobenzotriazole 1-oxide (Ph-DNBT, 2c). The observation that the most activated benzotriazole 1-oxide structure 2a which resembles 4,6-dinitrobenzofuroxan (DNBF) in superelectrophilic behaviour, is the only one that undergoes Diels–Alder reactions, points to a direct relationship between superelectrophilic and pericyclic reactivity.Key words: σ-complexes, arylnitrobenzotriazole 1-oxides, super-electrophiles, Diels–Alder condensations, pericyclic reactions.

The reaction of 4,6-dinitrobenzofuroxan (DNBF) with 1-trimethylsilyloxybuta-1,3-diene (8) is shown to afford a mixture of [2+4] diastereomeric cycloadducts (10, 11) through stepwise addition-cyclization pathways. Zwitterionic intermediate sigma-adduct 9, which is involved in the processes, has been successfully characterized by (1)H and (13)C NMR spectroscopy and UV/visible spectrophotometry in acetonitrile. A kinetic study has been carried out in this solvent that revealed that the rate of formation of 9 nicely fits the three-parameter equation log k=s(E+N) developed by Mayr to describe the feasibility of nucleophile-electrophile combinations. This significantly adds to the NMR spectroscopic evidence that the overall cycloadditions take place through a stepwise mechanism. The reaction has also been studied in dichloromethane and toluene. In these less polar solvents, the stability of 9 is not sufficient to allow direct characterization by spectroscopic methods, but a kinetic investigation supports the view that stepwise processes are still operating. An informative comparison of our reaction with previous interactions firmly identified as prototype stepwise cycloadditions is made on the basis of the global electrophilicity index, omega, defined by Parr within the density functional theory, and highlighted by Domingo et al. as a powerful tool for understanding Diels-Alder reactions.

Rate constants (k p B ,k -p BH ) for the reversible deprotonation of (2,2',2'',4,4',4''-hexanitrotriphenyl), (2,2',4,4',4''-pentanitrotriphenyl), (2,4,4',4''-tetranitrotriphenyl), and (4,4',4''-trinitrotriphenyl)methanes (la-d) by primary aliphatic amines and piperidine and morpholine as well as by phenoxide anion and hydroxide anion have been measred in 50% H 2 O-50% Me 2 SO and 20% H 2 O-80% Me 2 SO at 25 o C

The kinetics of sigma-complexation of 2,6-bis(trifluoromethanesulfonyl)-4-nitroanisole (4) have been investigated over a large pH range of 2-15.68 in methanol. Two competitive processes have been identified with the initial addition of MeO(-) at the unsubstituted 3-position of 4 to give a 1,3-dimethoxy adduct (4b-Me) and a subsequent and slow conversion of this species into the 1,1-dimethoxy isomer (4a-Me). Both 4a-Me and 4b-Me are more stable than the related adducts of 2,6-dinitro-4-trifluromethanesulfonylanisole, i.e.5a-Me and 5b-Me, and 2,4,6-trinitroanisole, i.e.6a-Me and 6b-Me, the latter compound being a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high thermodynamic stability of 4a-Me (pK(a) = 10.48) and 4b-Me (pK(a) = 12.23) relative to 5a-Me (pK(a) = 10.68) and 6a-Me (pK(a) = 12.56) or 5b-Me (pK(a) = 15.38) and 6b-Me (pK(a) = 16.46), is shown to derive from an especially high capacity of a para or an ortho SO(2)CF(3) group to stabilize a negative charge through Fpi-type polarization effects. From the kinetic data, it appears that the contribution of a methanol pathway to the formation of 4a-Me is much weaker than that found to operate in the formation of the 1,1-complex 5a-Me of 2,6-dinitro-4-trifluromethanesulfonylanisole, the experimental evidence suggesting that the reactivity of 4 and 5 is located just beyond the region defining the boundary between super- and normal-electrophilicity in methanol. Comparison of our results with available literature data show that this boundary corresponds to a pK(MeOH)(a) value of approximately 10, in agreement with our previous finding of a very effective solvent contribution to the sigma-complexation of 1,3,5-tris(trifluoromethanesulfonyl)benzene (13; pK(MeOH)(a) = 9.12) in methanol. Taking advantage of our observation that pK(MeOH)(a) and pK(H(2)O)(a) values for sigma-complexation at unsubstituted ring positions are related by a nice linear correlation, an approximate ranking of the electrophilicity of our aromatic triflones on the E scale developed by Mayr (Acc. Chem. Res. 2003, 36, 66) can be made.

The kinetics of the coupling of 4-nitrobenzodifuroxan (NBDF) with a series of indoles 8 a-e to give the expected Michael-type adducts 9 a-e have been investigated in acetonitrile solution. No significant influence of the nature of the isotopic substitution at C-3 of the indole ring has been found, indicating that the NBDF addition step is the rate limiting step of the SEAr substitution of the indole moiety. This implies that the measured second-order rate constants (k) for the reactions are identical to the second order rate constants (k1NBDF) associated to the C--C coupling step. By using the known N and s parameters characterizing the nucleophilicity of indoles, the k1NBDF rate constants are found to fit nicely to the three parameters equation logk1=s(N+E) introduced by Mayr to describe the feasibility of nucleophilic-electrophilic combinations. Based on this, the electrophilicity parameter E of NBDF could be determined as E=-6.15. This corresponds to a positioning of the reactivity of the nitroactivated double bond of NBDF in the domain of superelectrophilicity previously defined for nitrobenzofuroxans, in accord with the finding that the rates of coupling of 8 a-e with NBDF are only one order of magnitude lower than those for the coupling of these indoles with 4,6-dinitrobenzofuroxan (DNBF). The theoretical scale of electrophilicity introduced by Domingo et al. on the basis of the global electrophilicity index omega defined by Parr is also a very useful tool to discuss the relative reactivities of NBDF, DNBF, and a number of differently activated C==C double bonds.

The kinetics of the coupling of indole (1a), N-methylindole (1b), 5-methoxyindole (1c), and 5-cyanoindole (1d) with a set of reference benzhydryl cations have been investigated in acetonitrile and/or dichloromethane. The second-order rate constants for the reactions correlate linearly with the electrophilicity parameter E of the benzhydryl cations. This allows the determination of the reactivity parameters, N and s, characterizing the nucleophilicity of 1a-d according to the linear free enthalpy relationship log k(20 degrees C) = s(N + E) (Acc. Chem. Res. 2003, 36, 66). The nucleophilicity parameters thus defined describe nicely the reactions of 1a-d with 4,6-dinitrobenzofuroxan (2), a neutral superelectrophilic heteroaromatic whose electrophilicity (E) has been recently determined. On this ground, the kinetics of the coupling of 2 with a large variety of indole structures have been studied in acetonitrile, leading to a ranking of this family of pi-excessive carbon nucleophiles over a large domain of the nucleophilicity scale N. Importantly, two linear and parallel correlations are obtained on plotting the measured N values versus the pK(a)(H(2)O) values for protonation at C-3 of 5-X-substituted indoles and 5-X-substituted 2-methylindoles, respectively. This splitting reveals that the presence of the 2-methyl group causes steric hindrance to the approach of 2 from the adjacent C-3 position of an indole structure. The N vs pK(a)(H(2)O) correlation for 5-X-substituted indoles is used for a rapid determination of the C-3 basicity of indoles whose acidity constants cannot be measured through equilibrium studies in strongly acidic aqueous media.

A study of the dual electrophilic and pericyclic reactivity of 4,6-dinitrobenzofurazan (DNBZ, 2), 4,6-dinitro-2,1,3-benzothiadiazole (DNBS, 3), 4,6-dinitro-2,1,3-benzoselenadiazole (DNBSe, 4) is reported. Kinetic and thermodynamic measurements of the ease of covalent hydration of 2-4 to give the corresponding hydroxy sigma-adducts C-2-C-4 have been carried out over a large pH range in aqueous solution. Analysis of the data has allowed a determination of the rate constants k1(H2O) pertaining to the susceptibility of 2-4 to water attack as well as the pKa values for the sigma-complexation processes. With pKa values ranging from 3.92 for DNBZ to 6.34 for DNBSe to 7.86 for DNBS, the electrophilic character of the three heteroaromatics is much closer to that of the superelectrophilic reference, i.e. 4,6-dinitrobenzofuroxan (DNBF, 1; pKa = 3.75), than that of the standard Meisenheimer electrophile 1,3,5-trinitrobenzene (TNB, pKa = 13.43). Most importantly, water is found to be an efficient nucleophile which contributes strongly to the formation of the adducts C-2 and C-4. This confirms a previous observation that a pKa value of ca. 8 is a primary requirement for having H2O competing effectively as a nucleophile with OH- in the formation of hydroxy sigma-adducts. On the other hand, 2-4 are found to exhibit dienophilic and/or heterodienic behaviour on treatment with isoprene, 2,3-dimethylbutadiene, cyclopentadiene or cyclohexadiene, affording Diels-Alder mono- or di-adducts which have all been structurally characterized. A major finding is that the order of Diels-Alder reactivity follows clearly the order of electrophilicity, pointing to a direct relationship between superelectrophilic and pericyclic reactivity. This relationship is discussed.

A detailed thermodynamic and kinetic investigation of the reactions of 4,6-dinitrotetrazolo[1,5-a]pyridine (DNTP) with water and methanol has been made in the corresponding solvents. In aqueous solution, covalent addition of water to DNTP occurs with the exclusive formation of an anionic hydroxy σ-complex C-4a which is half-formed in a 0.4 M HCl solution (pKσa = 0.4). This corresponds to a 3 pK-units jump in thermodynamic stability from the most stable hydroxy σ-complex known so far, i.e. the hydroxy adduct C-3a of 4,6-dinitrobenzofuroxan (DNBF). DNTP forms similarly a very stable methoxy σ-complex C-4b in methanol (pKσa = 2.64). Interestingly, the addition of methanol to DNTP also results in the partial formation of a neutral carbinolamine-type adduct (C-5b) at low pH. Rate and equilibrium constants pertaining to most of the reaction pathways involved in the interactions have been determined. In particular, the following rate constants kH2O1 and kMeOH1 for formation of C-4a and C-4b have been measured: kH2O1 = 1.93 s−1; kMeOH1 = 3.50 s−1, to be compared with kH2O1 = 0.035 s−1; kMeOH1 = 0.030 s−1 for σ-complexation of DNBF under similar experimental conditions. Altogether, the results obtained reveal that DNTP is a considerably more powerful electrophile than DNBF, the common reference as to whether an electron-deficient aromatic or heteroaromatic substrate may be accorded superelectrophilic properties in addition or substitution processes.