Nucleophilicity of metal carbonyl anions in vinylic substitution reactions

Second order rate constants are reported for the reactions of metal carbonyl anions ([M(CO)_nL]^?) with several vinyl halides: PhCCl?C(CN)₂, Z‐ and E‐Ph(CN)C?CHHal (Hal = Cl, Br) which follow the addition–elimination (Ad_NE) substitution mechanism. The obtained data show that the nucleophilic reactivity of [M(CO)_nL]^? anions towards vinyl halides increases in the same order as in aliphatic S_N2 reactions, but much more steeply, by 14 orders of magnitude in the row log{ }: [CpFe(CO)₂]^? (～14), [Re(CO)₅]^? (7.8), [Mn(CO)₅]^? 2.1, [CpW(CO)₃]^? (0.7) > [CpMo(CO)₃]^? (0). A good correlation exists between nucleophilicities of [M(CO)_nL]^? anions towards vinyl (sp²‐carbon) and alkyl halides (sp³‐carbon) with slope 2.7. The reactivity of [M(CO)_nL]^? in a halogen–metal exchange process (with Z‐PhC(CN)?CHI) follows a similar ‘large’ scale as in the Ad_NE process. The nucleophilicity of [M(CO)_nL]^? anions correlates better with their one‐electron oxidation potentials (E_ox) than with their basicity (pK_a of [M(CO)_nL]H). Copyright © 2008 John Wiley & Sons, Ltd.     

Effect of the tether length upon Truce‐Smiles rearrangement reactions

This report examines the effect of substrate design upon the Truce‐Smiles rearrangement, an intramolecular nucleophilic aromatic substitution reaction. The length of the molecular spacer that tethers the carbanion nucleophile to the substituted benzene ring was found to have a strong influence on the ability of the substrate to undergo the reaction successfully. Our experimental results show highest yield of desired aryl migration product for substrates designed with a 3‐atom tether, which proceed through a 5‐membered spirocyclic intermediate. The results are interpreted in comparison with a survey of Truce‐Smiles rearrangements described in the literature and found to be consistent. Computational studies support the observed reactivity trend and suggest an explanation of a favorable combination of ring strain and electrostatic repulsion leading to optimal reactivity of the substrate designed with a 3‐atom tether. Comparison of our results with trends for related ring‐closing reactions illustrate the unique electrostatic features of the system studied herein.     

The influence of steric effects on the kinetics and mechanism of SNAr reactions of 1‐phenoxy‐nitrobenzenes with aliphatic primary amines in acetonitrile

Rate constants are reported for the reactions of 1‐phenoxy‐dinitrobenzenes, 3 , 1‐phenoxy‐dinitrotrifluoromethylbenzenes, 4 , with n‐propylamine, and 1‐methylheptylamine in acetonitrile as solvent. The results are compared with results reported previously for n‐butylamine, pyrrolidine, and piperidine. Decreasing ring activation leads to lower values of k₁ for nucleophilic attack although this may be mediated by reduced steric congestion around the reaction centre. Specific steric effects, leading to rate retardation, are noted for the ortho‐CF₃ group. In general, reactant‐bearing ortho‐CF₃ group were subject to base catalysis irrespective of the amine nucleophile and values of k_Am/k_?1 are reduced as the size of the amine get bulkier. This is likely to reflect increases in values of k_?1 coupled with decreases in values of k_Am as the proton transfer from zwitterionic intermediates to catalysing amine becomes less thermodynamically favourable.     

Kinetic study on the aromatic nucleophilic substitution reaction of 3,6‐dichloro‐1,2,4,5‐tetrazine by biothiols

The aromatic nucleophilic substitution reaction of 3,6‐dichloro‐1,2,4,5‐tetrazine (DCT) with a series of biothiols RSH: (cysteine, homocysteine, cysteinyl–glycine, N‐acetylcysteine, and glutathione) is subjected to a kinetic investigation. The reactions are studied by following spectrophotometrically the disappearance of DCT at 370 nm. In the case of an excess of N‐acetylcysteine and glutathione, clean pseudo first‐order rate constants (k_obs1) are found. However, for cysteine, homocysteine and cysteinyl–glycine, two consecutive reactions are observed. The first one is the nucleophilic aromatic substitution of the chlorine by the sulfhydryl group of these biothiols (RSH) and the second one is the intramolecular and intermolecular nucleophilic aromatic substitutions of their alkylthio with the amine group of RSH to give the di‐substituted compound. Therefore, in these cases, two pseudo first‐order rate constants (k_obs1 and k_obs2, respectively) are found under biothiol excess. Plots of k_obs1 versus free thiol concentration at constant pH are linear, with the slope (k_N) independent of pH (from 6.8 to 7.4). The kinetic data analysis (Brønsted‐type plot and activation parameters) is consistent with an addition–elimination mechanism with the nucleophilic attack as the rate‐determining step. Copyright © 2014 John Wiley & Sons, Ltd.     

Nucleophilic aromatic substitution in chlorinated aromatic systems with a glutathione thiolate model

The conjugation of glutathione with chlorobenzene and di‐, tri‐, tetra‐, and hexa‐chlorinated benzenes via nucleophilic aromatic substitution was modeled for isolated reacting species by ab initio molecular orbital theory to provide an understanding of the intrinsic reactivity of unactivated chloroaromatic systems. Computations at the HF/6‐31+G(d,p) level were augmented with electron correlation corrections using MP2 theory and density functional theory at the B3LYP level. Features of the reaction hypersurface were elaborated using thiolate (thiomethoxide) as the model for an enzyme‐activated glutathione molecule. Unlike the similar reaction with 1‐chloro‐2, 4‐dinitrobenzene a known substrate with glutathione, no σ‐complex or Meisenheimer complex was isolated as a true intermediate on the hypersurface. Instead, the σ‐complex appears as a transition state, preceded and followed by two ion‐molecule complexes in which the approaching and departing anions reside in the plane of the aromatic ring. Solvent calculations show a very similar hypersurface landscape with only one transition state and no intermediate. Activation energies are somewhat greater than for 1‐chloro‐2, 4‐dinitrobenzene owing to the lack of nitro substituents, which provide stabilization in these systems. Nevertheless, activation energies calculated at correlated levels indicate that these reactions are still feasible and consistent with experiment. Transition states and activation energies for dichlorobenzenes and polychlorobenzenes are lower in energy than for chlorobenzene implying greater stability conferred to the transition state by ortho and para substituents.     

Reaction kinetics investigation of 1‐fluoro‐2,4‐dinitrobenzene with substituted anilines in ethyl acetate–methanol mixtures using linear and nonlinear free energy relationships

Aromatic nucleophilic substitution reaction of 1‐fluoro‐2,4‐dinitrobenzene with para‐substituted and meta‐substituted anilines was kinetically investigated in the mixtures of ethyl acetate and methanol at room temperature. The correlation of second‐order rate coefficients with Hammett's substituent constants yields a fairly linear straight line with negative slope in different mole fractions of ethyl acetate–methanol mixtures. The measured rate coefficients of the reaction demonstrated a dramatic variation in ethyl acetate–methanol mixtures with the increasing mole fraction of ethyl acetate. Linear free energy relationship (LFER) investigations confirm that polarity has a major effect on the reaction rate whereas the hydrogen‐bonding ability of the media has a slight effect on it. Nonlinear free energy relationship based on preferential solvation hypothesis showed differences between the microsphere solvation of the solute and the bulk composition of the solvents, and non‐ideal behavior is observed in the trend of the rate coefficients, which cover the LFER results. Copyright © 2011 John Wiley & Sons, Ltd.     

The mechanism of aromatic nucleophilic substitution reaction between ethanolamine and fluoro‐nitrobenzenes: an investigation by kinetic measurements and DFT calculations

We have studied the kinetics and elucidated the mechanism by DFT calculation of the reaction between ethanolamine (EOA) and 1‐fluoro‐2,4‐dinitrobenzene (DNFB) in acetonitrile and toluene. To determine the contribution of the nitro group, the activation energy of the reaction between ethanolamine and 1‐fluoro‐2‐nitrobenzene (MNFB) vs. DNFB was determined in acetonitrile and calculated by DFT method. Kinetic measurements reveal that the reaction is faster in acetonitrile than in toluene. The reaction follows overall second‐order kinetics: first order with respect to both EOA and DNFB which is similar to the results reported for reaction between other primary amines and 1‐substituted‐2,4‐dinitrobenzenes. The calculations by using DFT methods reveal that the mechanism of the reaction involves the formation and decomposition of a Meisenheimer complex (MC). DFT calculations also reveal that the activation energy of the reaction is highest in vacuum and decreases with increasing polarity of the solvent reaching a minimum in acetonitrile. In addition, activation energies obtained by both DFT calculations and experiments show that the reactivity of MNFB is less than that of DNFB showing the effect of the 4‐nitro group. Copyright © 2010 John Wiley & Sons, Ltd.     

Computational studies of the effects of ortho‐ring and para‐ring activation on the kinetics of SNAr reactions of 1‐chloro‐2‐nitrobenzene and 1‐phenoxy‐2‐nitrobenzene with aniline

Computational studies are reported for reactions of 4‐substituted‐1‐chloro‐2,6‐dinitrobenzenes 1 , 6‐substituted‐1‐chloro‐2,4‐dinitrobenzenes 2 and some of the corresponding 1‐phenoxy derivatives 3 and 4 with aniline in the gas phase. The effects of substituent groups in the calculated energy values for reactants 1–4 , transition states structures, intermediates and products formed in the reactions between the compounds and anilines have been compared. Calculated bonds length and angles from optimized structures of the reactants were comparable with values reported for some of compounds 1–4 obtained by X‐ray crystal structures analysis. Generally, the decomposition of the Meisenheimer intermediate to the products requires more energy compared with the reactants except for when R = H. The order of stabilization of the intermediate was found to reflect the relative order of activation by substituents in the substrates. The 4‐substituted‐1‐chloro‐2,6‐dinitrobenzenes 1 and the phenoxy derivatives 3 were found to be more stable than their corresponding 6‐substituted analogues. This is an indication that the rate of nucleophilic attack at 1‐position will increase with increasing ring activation but may be reduced by steric repulsion at the reaction centre that increases in the order Cl < OPh. However, the steric hindrance to the steps involved in nucleophilic substitution by aniline is significantly increased when the substrates contain two ortho‐substituents. In most cases, the rate determining step is the decomposition of the σ‐adduct intermediate except with 1‐chloro‐2,6‐dinitrobenzenes 1 and 6‐substituted‐1‐chloro‐2,4‐dinitrobenzenes 2 , either because of reduction in ring activation or the presence of bulky ortho‐substituents in the chloro compounds 1 and 2 . Copyright © 2014 John Wiley & Sons, Ltd.     

Hydrogen‐bonded nucleophile effects in ANS: the reactions of 1‐chloro and 1‐fluoro‐2,4‐dinitrobenzene with 2‐guanidinobenzimidazole, 1‐(2‐aminoethyl)piperidine and N‐(3‐aminopropyl)morpholine in aprotic solvents

The kinetics of the reactions of 2,4‐dinitrofluorobenzene (DNFB) and 2,4‐dinitrochlorobenzene (DNClB) with 2‐guanidinobenzimidazole (2‐GB) at 40 ± 0.2 °C in dimethylsulphoxide (DMSO), toluene, and in toluene–DMSO mixtures, and with 1‐(2‐aminoethyl)piperidine (2‐AEPip) and N‐(3‐aminopropyl)morpholine (3‐APMo) in toluene at 25 ± 0.2 °C were studied under pseudo first‐order conditions. For the reactions of 2‐GB carried out in pure DMSO, the second‐order rate coefficients were independent of the amine concentration. In contrast, the reactions of 2‐GB with DNFB in toluene, showed a kinetic behaviour consistent with a base‐catalysed decomposition of the zwitterionic intermediate. These results suggest an intramolecular H‐bonding of 2‐GB in toluene, which is not present in DMSO. To confirm this interpretation the reactions were studied in DMSO–toluene mixtures. Small amounts of DMSO produce significant increase in rate that is not expected on the basis of the classical effect of a dipolar aprotic medium; the effect is consistent with the formation of a nucleophile/co‐solvent mixed aggregate. For the reactions of 3‐APMo with both substrates in toluene, the second‐order rate coefficients, k_A, show a linear dependence on the [amine]. 3‐APMo is able to form a six‐membered ring by an intramolecular H‐bond which prevents the formation of self‐aggregates. In contrast, a third order was observed in the reactions with 2‐AEPip: these results can be interpreted as a H‐bonded homo‐aggregate of the amine acting as a better nucleophile than the monomer. Most of these results can be well explained within the frame of the ‘dimer nucleophile’ mechanism. Copyright © 2010 John Wiley & Sons, Ltd.     

Nucleophilic substitution reactions promoted by oligoethylene glycols: a mechanistic study of ion‐pair SN2 processes facilitated by Lewis base

We present a mechanistic study for nucleophilic substitution (S_N2) reactions facilitated by multifunctional n‐oligoethylene glycols (n‐oligoEGs) using alkali metal salts MX (M⁺ = Cs⁺, K⁺, X^– = F^–, Br^–, I^–, CN^–) as nucleophilic agents. Density functional theory method is employed to elucidate the underlying mechanism of the S_N2 reaction. We found that the nucleophiles react as ion pairs, whose metal cation is ‘coordinated’ by the oxygen atoms in oligoEGs acting as Lewis base to reduce the unfavorable electrostatic effects of M⁺ on X^–. The two terminal hydroxyl (?OH) function as ‘anchors’ to collect the nucleophile and the substrate in an ideal configuration for the reaction. Calculated barriers of the reactions are in excellent agreement with all experimentally observed trends of S_N2 yields obtained by using various metal cations, nucleophiles and oligoEGs. The reaction barriers are calculated to decrease from triEG to pentaEG, in agreement with the experimentally observed order of efficiency (triEG < tetraEG < pentaEG). The observed relative efficiency of the metal cations Cs⁺ versus K⁺ is also nicely demonstrated (larger [better] barrier [efficiency] for Cs⁺ than for K⁺). We also examine the effects of the nucleophiles (F^–, Br^–, I^–, CN^–), finding that the magnitudes of reaction barriers are F^– > CN^– > Br^– > I^–, elucidating the observation that the yield was lowest for F^–. It is suggested that the role of oxygen atoms in the promoters is equivalent to that of –OH group in bulky alcohols (tert‐butyl or amyl‐alcohol) for S_N2 fluorination reactions previously studied in our lab. Copyright © 2012 John Wiley & Sons, Ltd.     

Aromatic nitro substitution reaction between 4‐nitro‐N‐n‐butyl‐1,8‐naphthalimide and n‐heptanethiol in water–methanol binary mixtures

The second‐order rate constants of thiolysis by n‐heptanethiol on 4‐nitro‐N‐n‐butyl‐1,8‐naphthalimide (4NBN) are strongly affected by the water–methanol binary mixture composition reaching its maximum at around 50% mole fraction. In parallel solvent effects on 4NBN absorption molar extinction coefficient also shows a maximum at this composition region. From the spectroscopic study of reactant and product and the known H‐bond capacity of the mixture a rationalization that involves specific solvent H‐donor interaction with the nitro group is proposed to explain the kinetic data. Present findings also show a convenient methodology to obtain strongly fluorescent imides, valuable for peptide and analogs labeling as well as for thio‐naphthalimide derivatives preparations. Copyright © 2008 John Wiley & Sons, Ltd.     

Kinetic studies of the reaction of phenacyl bromide derivatives with sulfur nucleophiles

The reaction of the substituted phenacyl bromides 1a–e and 2a–e with thioglycolic acid 3 and thiophenol 6 in methanol underwent nucleophilic substitution S_N2 mechanism to give the corresponding 2‐sulfanylacetic acid derivatives 4a–e, 5a–e and benzenethiol derivatives 9a–e, 10a–e. The reactants and products were identified by mass spectra, infrared and nuclear magnetic resonance. We measured the kinetics of these reactions conductometrically in methanol at a range of temperatures. The rates of the reactions were found to fit the Hammett equation and correlated with σ‐Hammett values. The ρ values for thioglycolic acid were 1.22–1.21 in the case of 4‐substituted phenacyl bromide 1a–e, while in the case of the nitro derivatives 2a–e they were 0.39–0.35. The ρ values for thiophenol were 0.97–0.83 in the case of 4‐substituted phenacyl bromide 1a–e, while in the case of the nitro derivatives 2a–e they were 0.79–0.74. The Brønsted‐type plot was linear with a α = ?0.41 ± 0.03. The kinetic data and structure‐reactivity relationships indicate that the reaction of 1a–e and 2a–e with thiol nucleophiles proceeds by a concerted mechanism. The plot of log k₄₅ versus log k₃₀, the plot log(k_x,3‐NO2/k_H) versus log(k_x/k_H), and the Brønsted‐type correlation indicate that the reactions of the thiol nucleophiles with the substituted phenacyl bromides 1a–e and 2a–e are attributed to the electronic nature of the substituents. Copyright © 2011 John Wiley & Sons, Ltd.     

Reactions of O‐aryl S‐aryl dithiocarbonates with secondary alicyclic amines in aqueous ethanol. Kinetics and mechanism

The reactions of O‐(4‐methylphenyl) S‐(4‐nitrophenyl), O‐(4‐chlorophenyl) (4‐nitrophenyl), O‐(4‐chlorophenyl) S‐phenyl, and O‐(4‐methylphenyl) S‐phenyl dithiocarbonates ( 1 , 2 , 3 , and 4 , respectively) with a series of secondary alicyclic (SA) amines are subjected to a kinetic investigation in 44 wt% ethanol‐water, at 25.0 °C and an ionic strength of 0.2 M. The reactions are followed spectrophotometrically. Under amine excess, pseudo‐first‐order rate coefficients (k_obs) are found. For some of the reactions, plots of k_obs vs. free amine concentration at constant pH are linear but others are nonlinear upwards. This kinetic behavior is in accordance with a stepwise mechanism with two tetrahedral intermediates, one zwitterionic (T^±) and the other anionic (T^?). In some cases, there is a kinetically significant proton transfer from T^± to an amine to yield T^?. Values of the rate micro constants k₁ (amine attack to form T^±), k_?1 (its back step), k₂ (nucleofuge expulsion from T^±), and k₃ (proton transfer from T^± to the amine) are determined for some reactions. The Brønsted plots for k₁ are linear with slopes β₁ = 0.2–0.4 in accordance with the slope values found when T^± formation is the rate‐determining step. The sensitivity of log k₁ and log k_?1 to the pK_a of the amine, leaving and non‐leaving groups are determined by a multiparametric equation. For the reactions of 1 – 4 with 1‐formylpiperazine and those of 3 and 4 with morpholine the k₂ and k₃ steps are rate determining. Copyright © 2010 John Wiley & Sons, Ltd.     

Steric effects on the mechanism of reaction of nucleophilic substitution of β‐substituted alkoxyvinyl trifluoromethyl ketones with four secondary amines

The kinetics of the reaction of β‐substituted β‐alkoxyvinyl trifluoromethyl ketones R¹O‐CR²?CH‐COCF₃ ( 1a – e ) [( 1a ), R¹?C₂H₅, R²?H; ( 1b ), R¹?R²?CH₃; ( 1c ), R¹?C₂H₅, R²?C₆H₅; ( 1d ), R¹?C₂H₅, R²?V^?pNO₂C₆H₄; ( 1e ), R¹?C₂H₅, R²?C(CH₃)₃] with four aliphatic amines ( 2a – d ) [( 2a ), (C₂H₅)₂NH; ( 2b ), (i‐C₃H₇)₂NH; ( 2c ), (CH₂)₅NH; ( 2d ), O(CH₂CH₂)₂NH] was studied in two aprotic solvents, hexane and acetonitrile. The least reactive stereoisomeric form of ( 1a – d ) was the most populated ( E‐s‐Z‐o‐Z ) form, whereas in ( 1e ), the more reactive form ( Z‐s‐Z‐o‐Z ) dominated. The reactions studied proceeded via common transition state formation whose decomposition occurred by ‘uncatalyzed’ and/or ‘catalyzed’ route. Shielding of the reaction centre by bulky β‐substituents lowered abruptly both k′ (‘uncatalyzed’ rate constant) and k″ (‘catalyzed’ rate constant) of this reaction. Bulky amines reduced k″ to a greater extent than k′ as a result of an additional steric retardation to the approach of the bulky amine to its ammonium ion in the transition state. An increase in the electron‐withdrawing ability of the β‐substituent increased ‘uncatalyzed’ k′ due to the acceleration of the initial nucleophile attack (k₁) and ‘uncatalyzed’ decomposition of transition state (k₂) via promoting electrophilic assistance (through transition state 8 ). The amine basicity determined the route of the reaction: the higher amine basicity, the higher k₃/k₂ ratio (a measure of the ‘catalyzed’ route contribution as compared to the ‘uncatalyzed’ process) was. ‘Uncatalyzed’ route predominated for all reactions; however in polar acetonitrile the contribution of the ‘catalyzed’ route was significant for amines with high pK_a and small bulk. Copyright © 2007 John Wiley & Sons, Ltd.     

Reactivity of sodium arenesulfinates in the substitution reaction to γ‐functionalized allyl bromides

The kinetics of nucleophilic bimolecular substitution reactions of γ‐functionalized allyl bromides with non‐substituted and p‐substituted sodium arenesulfinates has been studied. Both the structure of allyl bromides and nucleophilicity of arenesulfinate ions exerted a significant effect on the values of the kinetic parameters such as the second‐order rate constants k, activation energy E_A, and changes in the entropy ΔS^≠, enthalpy ΔH^≠, and free energy ΔG^≠ of the formation of the activated complex from reactants. Based on the evaluation of kinetic parameters, the reactants could be arranged, according to their decreasing reactivity in the S_N2‐reactions as follows: p‐toluenesulfinate ion > benzenesulfinate ion > p‐chlorobenzenesulfinate ion and 4‐bromo‐2‐butenenitrile > 1,3‐ dibromopropene, respectively. Comparison was also made between the kinetic data obtained and some delocalization reactivity indexes for both the substrates and nucleophiles. The enthalpy–entropy compensation effect was observed for the reactions of sodium arenesulfinates with γ‐functionalized allyl bromides. Copyright © 2009 John Wiley & Sons, Ltd.     

Kinetics and mechanism of the reactions of O‐aryl S‐(4‐nitrophenyl) dithiocarbonates with anilines in aqueous ethanol

The reactions of O‐(4‐methylphenyl) S‐(4‐nitrophenyl) dithiocarbonate and O‐(4‐chlorophenyl) S‐(4‐nitrophenyl) dithiocarbonate with a series of anilines are subjected to a kinetic investigation in 44 wt% ethanol–water, at 25.0 °C and an ionic strength of 0.2 M. The reactions are followed spectrophotometrically at 420 nm (appearance of 4‐nitrobenzenethiolate anion). Under excess amine, pseudo‐first‐order rate coefficients (k_obs) are found. For the reactions of both substrates with anilines, plots of k_obs versus free amine concentration at constant pH are nonlinear upwards, according to a second‐order polynomial equation. This kinetic behavior is in agreement with a stepwise mechanism consisting of two tetrahedral intermediates, one zwitterionic (T^±) and the other anionic (T^?), with a kinetically significant proton transfer from T^± to an aniline to yield T^?. The rate equation was derived from the proposed mechanism. By nonlinear least‐squares fitting of the rate equation to the experimental data, values of the rate micro‐coefficients involved in both steps were determined. Copyright © 2009 John Wiley & Sons, Ltd.     

Enantio‐differentiating reactions of a racemic γ‐lactone enolate with chiral esters. A DFT investigation

The acylation of lithium (±)‐spiro‐γ‐lactone enolate 5 by the O‐protected methyl (?)‐(S)‐lactate or the O‐protected methyl (+)‐(S)‐mandelate occurs through enantio‐differentiating reactions. The (S,S)‐enolate 5 is the most reactive with the lactate whereas the (R,R)‐enolate 5 selectively reacts with the mandelate. According to theoretical calculations at the B3LYP/6‐31G(++)(d,p) level of theory of 40 intermediates of this Claisen condensation, the experimental results are compatible with a previous chelation of the ester by an auxiliary cation lithium arising from the medium. The addition reaction occurs through a chelation process mediated by the counterion of the enolate. More stable tetrahedral intermediates including two lithium cations result from an antiperiplanar transition state. These results clearly demonstrate that the presence of a second lithium cation (the first lithium cation is solvated by di‐isopropylamine and the second one is solvated by a THF molecule or a di‐isopropylamide anion) stabilizes the tetrahedral intermediate and is compatible with an antiperiplanar transition state according to the Felkin–Anh model. Copyright © 2010 John Wiley & Sons, Ltd.     

Reactions of O‐aryl S‐aryl dithiocarbonates with pyridines in aqueous ethanol: kinetics and mechanism

The reactions of O‐(4‐methylphenyl) S‐(4‐nitrophenyl) dithiocarbonate ( 1 ), O‐(4‐chlorophenyl) S‐(4‐nitrophenyl) dithiocarbonate ( 2 ), and O‐(4‐chlorophenyl) S‐phenyl) dithiocarbonate ( 3 ) with a series of pyridines were subjected to a kinetic investigation in 44 wt% ethanol–water, at 25.0 °C and an ionic strength of 0.2 M. The reactions were followed spectrophotometrically. Under amine excess, pseudo‐first‐order rate coefficients (k_obs) were determined. For the studied reactions, plots of k_obs versus free pyridine concentration at constant pH were linear, with the slope (k_N) independent of pH. The Brønsted‐type plots for ( 1 ) and ( 2 ) were biphasic, suggesting a stepwise mechanism with a change in the rate‐determining step, from breakdown to the formation of a tetrahedral intermediate (T^±), as the basicity of the pyridines increases. For the reactions of ( 3 ), at the pK_a range of the pyridines studied, only the breakdown to products of T^± was observed. Copyright © 2009 John Wiley & Sons, Ltd.     

The nature of the electronic factor governing diastereofacial selectivity in remotely substituted (X) 2‐adamantyl cations: 5‐X versus 4‐X substitution

A limited series of 4^eq‐substituted (X) 2‐methyleneadamantanes ( 6 , Y?CH₂, X?F, Cl, Br, I, and SnMe₃) has been synthesized and diastereoselectivities for their hydrochlorination (HCl/CH₂Cl₂) have been determined. Diastereoselectivities for the fluorination (DAST/CH₂Cl₂) of secondary alcohol mixtures, obtained from the hydride reduction of the precursor ketones ( 6 ,Y?O) to the alkenes, have also been measured. A comparison of this selectivity data for nucleophilic trapping of 4^eq‐substituted (X) 2‐adamantyl cations ( 4 , R?H and Me) with the corresponding information for 5‐substituted (X) 2‐adamantyl cations ( 1 , R?H and Me) has revealed important distinctions between the two series. In particular, whereas extended hyperconjugative effects appear to be the predominant electronic effect governing facial selectivity in the 5,2‐series, electrostatic influences prevail in the 4,2‐disposition. Copyright © 2007 John Wiley & Sons, Ltd.