The influence of some steric and electron effects on the mechanism of aromatic nucleophilic substitution (SNAr) reactions in nonpolar solvent

Kinetic studies are reported for the reactions with aniline in benzene of a series of X‐phenyl 2,4,6‐trinitrophenyl ethers [X = H; 2‐, 3‐, 4‐CH₃; 2,4‐, or 2,6‐(CH₃)₂] a–f , and the results compared with those of the corresponding nitro derivatives. In the methyl series, kinetic data show that increasing substitution reduces drastically the rates of reactions indicative of the operation of some kind of steric effect. The unfavorable steric congestion at the reaction center appears to be unimportant in determining the kinetic order of the reactions. In general, the second‐order rate constants k_A depend linearly on the square of nucleophile concentration. The change in the kinetic form observed in the nitro derivatives may be largely due to the electron‐withdrawing effect of the group. With the 2,6‐dinitro derivative, however, the uncatalyzed pathway k₂ takes all the reaction flux. Steric hindrance to intermolecular proton transfer from base to the ethereal oxygen of the intermediate is sufficient to make the base‐catalyzed pathway insignificant relative to the k₂ pathway. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 744–750, 2005     

Aryl- and hetaryl-containing amide anions in reactions of aromatic nucleophilic substitution

The results of kinetic studies of S_NAr reactions ofp-nitrohalobenzenes, hexafluorobenzene, and pentafluoropyridine with aryl-, diaryl-, and hetarylamide anions under homogeneous conditions (in dimethyl sulfoxide) and under conditions of phase transfer catalysis (in toluene) are analyzed. The increase in the Brönsted coefficient _Nu in reactions of amide anions in DMSO as the electrophilicity of the substrate increases and steric hindrance in nucleophiles decreases may result from a higher degree of charge transfer from a nucleophile to a substrate in the transition state. The possibility of replacement of the S_NAr by the SET mechanism in these reaction is discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2315–2319, December, 1995.     

Relative reactivity and kinetic pattern of aniline and N‐methylaniline as nucleophiles in aromatic substitution (SNAr) reactions

Kinetic results are reported for the reactions of 4‐nitrophenyl‐2,4,6‐trinitrophenyl ether 3 with aniline and N‐methylaniline in dimethyl sulphoxide, acetonitrile, methanol, and benzene. The reactions gave the expected 2,4,6‐trinitrodiphenylamine and were base catalyzed in all the solvents. Both nucleophiles showed the same kinetic pattern under the same reaction conditions but aniline was found to be considerably more reactive than N‐methylaniline. The greater catalytic efficiency of aniline over N‐methylaniline is consistent with the proton transfer mechanism of the base‐catalyzed step. Dichotomy of amine effects in aromatic substitution (S_NAr) reactions is discussed. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 188–196, 2004     

Solvent effect on reversible self-termination reactions of aromatic free radicals

Rates and thermodynamic data have been obtained for the reversible self-termination reaction: Involving aromatic 2-(4′dimethylaminophenyl)indandione-1,3-yl (I), 2-(4′diphenylaminophenyl)indandione-1,3-yl (II), and 2,6 di-tert-butyl-4-(β-phthalylvinyl)-phenoxyl (III) radicals in different solvents. The type of solvent does not tangibly affect the 2k₁ of Radical(I), obviously due to a compensation effect. The log(2k₁) versus solvent parameter E_T(30) curves for the recombination of radicals (II) and (III) have been found to be V shaped, the minimum corresponding to chloroform. The intensive solvation of Radical (II) by chloroform converts the initially diffusion-controlled recombination of the radical into an activated reaction. The log (2k_?1) of the dimer of Radical (I) has been found to be a linear function of the Kirkwood parameter (ε - 1)/(2ε + 1), the dissociation rate increasing with the dielectic constant of the solvent. The investigation revealed an isokinetic relationship for the decay of the dimer of Radical (I), an isokinetic temperature β = 408 K and isoequilibrium relationship for the reversible recombination of Radical (I) with β° = 651 K. For Radical (I) dimer decay In(2k_?1) = const + 0.8 In K, where K is the equilibrium constant of this reversible reaction. The transition state of Radical (I) dimer dissociation reaction looks more like a pair of radicals than the initial dimer. The role of specific solvation in radical self-termination reactions is discussed.     

A Complication in the thermal reactions of 1,1,2,2-tetramethylcyclopropane

Reinvestigation of the gas phase thermal reaction of 1,1,2,2-tetramethylcyclopropane (699-759°K) gave for the unimolecular disappearance of reactant, k_(TMC) = 10^{15.27–63.93/θ} sec^?1, in good agreement with the original results of Frey and Marshall. However, evidence for a high activation energy (E = 79 ± 5 kcal/mole), competitive unimolecular decomposition to 2,3-dimethyl-1 and -2-butenes was also obtained. It is proposed that the serious discrepancy noted [1] between the experimentally observed Arrhenius parameters for the overall reaction kinetics, and those predicted by transition state calculations assuming a biradical mechanism for the isomerization reactions (previously believed to be the only primary reaction mode) can be explained in terms of the increasing importance of the decomposition reactions at higher reaction temperatures.     

Kinetics and mechanism of the aminolysis of O-ethyl S-phenyl dithiocarbonate in aqueous ethanol

The reactions of secondary alicyclic amines with the title substrate (PDTC) are subjected to a kinetic study in 44 wt.% aqueous ethanol, 25.0°C, ionic strength 0.2 M (KCl). Pseudo-first-order rate coefficients (k_obs) are found under amine excess. Linear plots of [N]/k_obs against 1/[N], where N is the free amine, are obtained for the reactions with piperidine, piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine. The reaction with 1-formylpiperazine exhibits a linear plot of k_obs against [N]². These results are interpreted through a mechanism consisting of two tetrahedral intermediates: a zwitterionic ( T ^±) and an anionic ( T ^?), where the amine catalyzed proton transfer from T ^± to T ^? is partially rate determining for the four former reactions and is fully rate determining for the reaction of 1-formylpiperazine. The rate microcoefficients involved in the reaction scheme are either determined experimentally or estimated. Comparison with the corresponding microcoefficients reported for the same reactions in water reveals that the rate coefficient for formation of T ^± from reactants (k₁) is smaller and that for the reversal of this (k_?1) is larger in aqueous ethanol compared to water, in agreement with the expected structure of the corresponding transition state. Bronsted-type plots are obtained for k₁, k_?1, and K₁ (=k₁/k_?1) with slopes ca. 0.4, ?0.6, and 1.0, respectively. Comparison of the present stepwise reactions with the concerted ones found in the same aminolysis of O-ethyl 2,4,6,-(trinitrophenyl) dithiocarbonate indicates that T ^± is so destabilized by the change of PhS by the 2,4,6-trinitrobenzenethio group that T ^± no longer exists and becomes a transition state. © 1995 John Wiley & Sons, Inc.     

Arrhenius constants for the reactions of ozone with ethylene and acetylene

The kinetics of ozonation of C₂H₄ and C₂H₂ have been studied in the gas phase from ?40 to ?95°C (C₂H₄) and +10 to ?30°C (C₂H₂). The O₃ concentrations were near 10^?4 M, and the hydrocarbons were present in 2- to 25-fold excess. A few experiments with propylene were also carried out. The reactions were followed by observing the rate of decay of O₃ absorption at 2537 Å. Reaction stoichiometries and effects of added O₂ were investigated. The second-order rate constant for C₂H₄ was log k(M^?1 sec^?1) = (6.3 ± 0.2) – (4.7 ± 0.2)/θ (θ = 2.3RT). The rate was independent of the presence of excess O₂. Rate measurements for C₃H₆ were less accurate because of aerosol interference. Combined with room temperature measurements of other workers, the C₃H₆ rate constant was log k(M^?1 sec^?1) = (6.0 ± 0.4) – (3.2 ± 0.6)/θ. The C₂H₂ rate constant was log k(M^?1 sec^?1) = (9.5 ± 0.4) – (10.8 ± 0.4)/θ. In the case of C₃H₆ the major product was propylene ozonide. Ethylene did not yield the ozonide, and the products of the O₃–C₂H₄ and O₃–C₂H₂ reactions were not identified. Pre-exponential factors for the olefin reactions are consistent with a five-membered ring transition state formed by 1,3 dipolar cycloaddition of O₃. For C₂H₂, however, the much higher observed A factor suggests a different mechanism. Possible transition states for the O₃–C₂H₂ reaction are discussed.     

A kinetic model for steric hindrance effects on quaternization of poly(vinylpyridines)

Quaternization reactions of poly(vinylpyridines) with alkyl halides show retardation in excess of that predicted by the classical second-order kinetics. Based on the classical collision and transition state theories, a kinetic model has been developed to quantify such retardation, in which the overall reaction rate is characterized by a rate constant k₀ of the intrinsic reactivity between a pyridyl group and an alkyl halide group, and by a steric hindrance effect parameter α. The latter accounts for the degree to which the rate of collisions of reactants is reduced, or to which the freedom of movement of the reactants in the transition state is restricted as the reaction proceeds. The resulting kinetic expression has been validated using experimental results reported in the literature and those of our own. The functional dependence of k₀ and α values on the nature of poly(vinylpyridines) and that of alkyl halides is explained. Other factors affecting k₀ and α, including changes in macromolecular dimensions and/or in the distribution of residue environment, quality of solvent, and reaction temperature, are discussed. © 1993 John Wiley & Sons, Inc.     

The reactions of hydrogen atoms with bis(trifluoromethyl)disulfide

The reactions of hydrogen atoms produced by the mercury-photosensitized decomposition of H₂ with bis(trifluoromethyl)disulfide has been studied. The rate coefficient for the primary reaction, H + CF₃SSCF₃ → CF₃SH + CF₃S, was determined in competition with the reaction H + C₂H₄S → SH + C₂H₄ to have the value k = (3.0 ± 0.18) × 10¹⁴ exp[-(4560 ± 140)/RT] cm³ mol^?1 S^?1. The high A factor can be partially accounted for by assuming free rotation for the two CF₃ groups and the SCF₃ groups about the S—S bond in the transition state. The relatively high activation energy is attributed to inductive and orbital overlap effects. CH₃SH, H₂S, and CF₃SH all react with CF₃SSCF₃ to yield solid complexes which were not explored further.     

Separation of polar and steric effects on absolute rate constants and arrhenius parameters for the reaction of tert-butyl radicals with alkenes

Absolute rate constants and their temperature dependencies were measured for the reaction of tert-butyl radicals with 24 substituted ethenes and several other compounds in 2-propanol solution by time-resolved electron spin resonance. At 300 K the rate constants cover the range from 60 M^?1 s^?1 (1,2-dimethylene) over 16,500 M^?1 s^?1 (vinyl-chloride) to 460,000 M^?1 s^?1 (2-vinylpyridine). For the mono- and 1,1-disubstituted ethenes log k₃₀₀ increases and the activation energy decreases with increasing electron affinity of the olefins. The frequency factors are in the range log A/M^?1 s^?1 = 7.5 ± 1.0 as typical for addition reactions, with minor exceptions. Electron affinity (polar) and steric effects on reactivity are separated for the addition of tert-butyl to chloro- and methyl-substituted ethylenes. A comparison with rate data for methyl, ethyl, 2-propyl, and other radicals indicates both polar and steric effects on radical substitution.     

Enantioselective syntheses of (E)-γ,δ-disubstituted homoallylic alcohols via BF3·OEt2-catalyzed aldehyde allylboration and analysis of the origin of E-selectivity: A1,2 allylic strain vs. syn-pentane interaction

Enantioselective allylboration of aldehydes with α-substituted β-methyl allylboronate was reported. By using BF₃·OEt₂ as the catalyst, γ,δ-disubstituted homoallylic alcohols were obtained in good yields with high E-selectivities and enantioselectivities. Transition state analysis revealed that the disfavored transition state suffers from a syn-pentane interaction between the BF₃ catalyst and axially oriented α-substituent of the allylboron reagent. Such a syn-pentane interaction is severe enough to overcome the A^1,2 allylic strain between the β-methyl group and the α-substituent of the boron reagent that is present in the favored competing transition state. Consequently, the reaction proceeded with equatorial placement of the α-substituent to furnish γ-methyl substituted homoallylic alcohols with high E-selectivity.     

Solvent effects on kinetics of an aromatic nucleophilic substitution reaction in mixtures of an ionic liquid with molecular solvents and prediction using artificial neural networks

Kinetics of the reaction between 1‐chloro‐2,4‐dinitrobenzene and aniline was studied in mixtures of 1‐ethyl‐3‐methylimidazolium ethylsulfate ([EMIM][EtSO₄]) with methanol, chloroform, and dimethylsulfoxide at 25°C. Single‐parameter correlations of log k_A versus normalized polarity parameter (E^N_T), hydrogen‐bond acceptor basicity (β), hydrogen‐bond donor acidity (α), and dipolarity/polarizability (π*) of media do not give acceptable results. Multiparameter linear regression (MLR) of log k_A versus the solvatochromic parameters demonstrates that the reaction rate constant increases with E^N_T, π*, and β and decreases with α parameter. To predict accurately solvent effects on the rate constant, optimized artificial neural network with three inputs (including α, π*, and β parameters) was applied for prediction of the log k_A values in the prediction set. It was found that properly selected and trained neural network could fairly represent the dependence of the reaction rate constant on solvatochromic parameters. Mean percent deviation of 5.023 for the prediction set by the MLR model should be compared with the value of 0.343 by the artificial neural network model. These improvements are due to the fact that the reaction rate constant shows nonlinear correlations with the solvatochromic parameters. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 153–159, 2009     

Substituent effects on the reactions of aromatic triflones with para‐X‐anilines in methanol: Low intrinsic reactivity and transition state imbalances

A kinetic study is reported for S_NA_r 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 β_X=0.57, α_Z=0.31, and an imbalance of I = α_Z–β_X=?0.26. The imbalance shows that resonance development lags behind C? N bond formation at the transition state. Interestingly, analysis of the results in terms of Marcus theory reveals that these S_NAr are associated with some extremely low intrinsic reactivity (log k_o=?1.25& © 2011 Wiley Peiodicals, Inc. Int J Chem Kinet 43: 255–262, 2011     

Competitive unimolecular reactions at low pressures. The pyrolysis of cyclobutyl chloride

The thermal decomposition of cyclobutyl chloride has been investigated over the temperature range of 892–1150 K using the technique of very low-pressure pyrolysis (VLPP). The reaction proceeds via two competitive unimolecular channels, one to yield ethylene and vinyl chloride and the other to yield 1,3-butadiene and hydrogen chloride, with the latter being the major reaction under the experimental conditions. With the usual assumption that gas-wall collisions are «strong,» RRKM calculations, generalized to take into account two competing pathways, show that the experimental unimolecular rate constants are consistent with the high-pressure Arrhenius parameters given by log k₁(sec^?1) = (14.8 ± 0.3) ? (61.1 ± 1.0)/Θ for vinyl chloride formation and log k₂(sec^?1) = (13.6 ± 0.3) ? (55.7 ± 1.0)/Θ for 1,3-butadiene formation, where Θ = 2.303 RT kcal/mol. The A factors were assigned from previous high-pressure low-temperature data of other workers assuming a four-center transition state for 1,2-HCl elimination and a chlorine-bridged biradical transition state for vinyl chloride formation. The activation energies are in good agreement with the high-pressure results which were obtained with a conventional static system. The difference in critical energies is 4.6 kcal/mol.     

The relative reactivity of primary and secondary amine hydrogen atoms of aromatic amines with epichlorohydrin and N- and O-glycidyl compounds

The relative value of the rate constants for the reactions between the secondary and primary amine hydrogen atoms of 3-trifluoromethylaniline with epichlorohydrin, and of aniline with phenyl glycidyl ether and with some N-alkyl-N-glycidylanilines were determined by HPLC analysis. Values ranged from 0.14 to 0.24 and are in agreement with the findings of earlier workers for the reactions of aromatic amines with O-glycidyl compounds but in direct conflict with the claim of a recent publication. The value for the reaction between 3-trifluoromethylaniline and epichlorohydrin was unaffected by the nature of the catalyst, which covered a wide range of strengths and steric requirements.     

Study of the reactions of cisplatin with ranitidine and nizatidine by means of 1H NMR spectroscopy in D2O

The reactions of cisplatin with nizatidine and ranitidine were studied in D₂O at pD 7.4 and 298 K by means of ¹H NMR spectroscopy. The second order rate constants, k ₂, for the reaction of cisplatin with nizatidine is (2.71 ± 0.11) × 10⁻⁴ M ⁻¹ s⁻¹, and for the reaction with ranitidine (6.72 ± 0.17) × 10⁻⁴ M ⁻¹ s⁻¹. The reactions of nizatidine and ranitidine were also studied with other Pd(II) and Pt(II) complexes. The set of the complexes was selected because of their difference in reactivity, steric hindrance, and binding properties. Correspondence: Prof. Dr. Živadin D. Bugarčić, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia.     

The kinetics of the gas phase intramolecular elimination of isobutene from 2-d1-triisobutylaluminum and the deuterium isotope effect in reactions involving cyclic transition states

The intramolecular elimination of isobutene from 2-d₁-triisobutylaluminum has been studied in the gas phase for temperatures ranging between 102.4 and 184.6°C. The reaction is apparently homogeneous and obeys the first order rate law, yielding the following Arrhenius relationship: Excess ethylene was added to the starting material in order to avoid complications from the backreaction. The cyclic 4-center nature of the transition state proposed earlier has been unequivocally demonstrated by deuterium labelling. Mass-spectral analyses show that the isobutene formed contains no deuterium. The hydrolyses products of the mixed trialkylaluminum formed during the reaction consist of monodeuteroethane and 2-d₁-isobutane. The observed negative entropy of activation of ～12 cal/°-mole agrees with prediction and implies a reasonably tight transition state structure. Combined with the corresponding data for the non deuterized Al(i-bu)₃ reported earlier, these data result in a primary kinetic deuterium isotope effect of k_H/k_D = 1.3 × 10^0.6/θ corresponding to a ratio of the isotopic rate constants of 3.7 at 25°C. This result is in excellent agreement with a predicted value of 1.4 × 10^0.7/θ and it is in line with literature data on similar reactions involving cyclic transition state complexes.     

An investigation of Prussian Blue analogues by Mössbauer spectroscopy and magnetic susceptibility

The Mössbauer spectra and magnetic susceptibilities have been obtained for a series of Prussian Blue analogues of general formula M_j^A[M^B(CN)₆]_k·mH₂O where M^A and M^B are transition metal ions, j and k vary with the oxidation states of M^A and M^B and m typically has values from 8 to 14. The compounds were prepared from the hexacyano acids or with large quaternary ammonium counterions and are therefore not contaminated with alkali cations. In each analogue, A or B is iron and the second metal is Mn, Cu, Co, Cr or Ru. In each case it was possible to assign the site (A or B), oxidation state and spin state to each transition metal ion. This group of compounds are all class II mixed valence species from their colours, but do not show evidence of linkage isomerism or redox changes compared to the starting materials. The Mössbauer linewidths are consistent with the Ludi model of Prussian Blue.     

Rate constants for some reactions of inorganic radicals with inorganic ions. Temperature and solvent dependence

Rate constants for several reactions of inorganic radicals with inorganic anions in aqueous and aqueous/acetonitrile solutions have been measured as a function of temperature by laser flash photolysis. The reactions studied were (1) Cl₂^? + N₃^?, (2) Br₂^? + N₃^?, (3) Cl₂^? + SCN^?, (4) Br₂^? + SCN^?, (5) SO₄^? + Cl^?, (6) SO₄^? + CO₃^2?, and (7) N₃? + I^?. The rate constants were corrected for ionic strength and ranged from 10⁶ to 10⁹ L mol^?1 s^?1. The Arrhenius activation energies varied from 2 to 12 kJ mol^?1 for the first 4 reactions, were higher for reaction 6, and negative for reaction 5. The pre-exponential factors also varied considerably with log A ranging from 5 to 14. The values of k₂₉₈ decreased in most cases by more than an order of magnitude upon increasing the acetonitrile (ACN) fraction from 0 to 70%. For most reactions, this decrease in k₂₉₈ was due to changes in log A with little regularity in the small changes observed in E_a. For reaction 7, k₂₉₈ was practically unchanged due to compensating effects of the changes in E_a and log A with ACN mol fraction, giving an isokinetic relationship. An isokinetic relationship was also observed in the case of reaction 6; E_a and log A change in parallel while changing ACN mol fraction. Reaction 3 (Cl₂^? + SCN^?) was also studied in water/t-butanol and water/acetic acid mixtures. Linear correlation was found between log k and the dielectric constant of the medium for water/ACN and water/t-BuOH but the lines for the two solvent mixtures had different slopes, suggesting specific solvation effects in addition to the primary solvent polarity effects. With water/acetic acid, k decreased and then increased upon addition of acetic acid. © 1993 John Wiley & Sons, Inc.     

Stereochemistry of the σ-Complex Intermediate in Sterically Hindered Electrophilic Aromatic Substitutions. (20th communication on diazo coupling reactions)

The kinetics of the diazo coupling reactions of diazotized sulfanilic acid with 9 derivatives of 2-naphthol, each containing a substituent in the 8-position, have been measured. The reactions proceed by general base catalysis. The rate constants (k₁) for the formation of the steady-state intermediate in the presence of varying concentrations of a base (pyridine) have been evaluated from rate measurements. Similarly the ratios k₂/k₁ (where k₂ is the rate constant for proton transfer from the steady-state intermediate to the base, and k_?1 is the rate constant for the dissociation of the intermediate) have been determined. The dependence of logk₁ on σ⁺_m and of the ratio k₂/k_?1 on a steric parameter R^f (defined in this paper) is interpreted as evidence for the steady-state intermediate existing as a benzodienone σ-complex with the sp³-bound hydrogen in a pseudo-equatorial position and the electrophile pseudo-axial. A sterically caused destabilisation of the intermediate can be excluded. The steric influence on the ratio k₂/k_?1 is therefore due to the steric influence on k₂ only. Diazo coupling of 8-(2′-pyridyl)-2-naphthol is subject to intramolecular base catalysis, as demonstrated by kinetic hydrogen isotope effects.