Curved Hammett plot in alkaline hydrolysis of O-aryl thionobenzoates: change in rate-determining step versus ground-state stabilization

Second-order rate constants have been measured for alkaline hydrolysis of O-aryl thionobenzoates (X-C(6)H(4)-CS-OC(6)H(4)-Y) in 80 mol % H(2)O-20 mol % DMSO at 25.0 +/- 0.1 degrees C. The Hammett plot for the reaction of O-4-nitrophenyl X-substituted thionobenzoates (X-C(6)H(4)-CS-OC(6)H(4)-NO(2), 1a-e) exhibits a downward curvature. However, a possible traditional explanation in terms of a change in the rate-determining step (RDS) has been considered but rejected. The proposed explanation involves stabilization of the ground-state (GS) through-resonance interaction between the electron-donating substituent X and the thionocarbonyl functionality on the basis of the linear Yukawa-Tsuno plot obtained for the same reaction. The Br?nsted-type plot for the reaction of O-aryl thionobenzoates (C(6)H(5)-CS-OC(6)H(4)-Y, 2a-i) is linear but exhibits many scattered points with a small beta(lg) (-0.35). The Hammett plot for the same reaction shows rather poor correlation with sigma(-) constants but much better correlation with sigma(o) constants. The alkaline hydrolysis of O-aryl thionobenzoates (1a-e and 2a-i) has been proposed to proceed through an addition intermediate in which bond formation is the RDS.     

Shift of the rate-determining step in a consecutive chemical reaction with variation of the reaction affinity

A consecutive single-route reaction is considered. When two (groups of) steps compete in controlling the overall reaction rate, there exists a general rule that the earlier step in the flow of the overall reaction tends to be rate-determining with the increase of the reaction affinity. The latter may, however, be distributed more or less evenly to both steps.     

Aminolysis of 2,4-dinitrophenyl X-substituted benzoates and Y-substituted phenyl benzoates in MeCN: effect of the reaction medium on rate and mechanism

Second‐order rate constants (k_N) have been determined spectrophotometrically for the reactions of 2,4‐dinitrophenyl X‐substituted benzoates ( 1 a – f ) and Y‐substituted phenyl benzoates ( 2 a – h ) with a series of alicyclic secondary amines in MeCN at 25.0±0.1 °C. The k_N values are only slightly larger in MeCN than in H₂O, although the amines studied are approximately 8 pK_a units more basic in the aprotic solvent than in H₂O. The Yukawa–Tsuno plot for the aminolysis of 1 a – f is linear, indicating that the electronic nature of the substituent X in the nonleaving group does not affect the rate‐determining step (RDS) or reaction mechanism. The Hammett correlation with σ^? constants also exhibits good linearity with a large slope (ρ_Y=3.54) for the reactions of 2 a – h with piperidine, implying that the leaving‐group departure occurs at the rate‐determining step. Aminolysis of 2,4‐dinitrophenyl benzoate ( 1 c ) results in a linear Brønsted‐type plot with a β_nuc value of 0.40, suggesting that bond formation between the attacking amine and the carbonyl carbon atom of 1 c is little advanced in the transition state (TS). A concerted mechanism is proposed for the aminolysis of 1 a – f in MeCN. The medium change from H₂O to MeCN appears to force the reaction to proceed concertedly by decreasing the stability of the zwitterionic tetrahedral intermediate (T^±) in aprotic solvent.     

The initial step of silicate versus aluminosilicate formation in zeolite synthesis: a reaction mechanism in water with a tetrapropylammonium template

The initial step for silicate and aluminosilicate condensation is studied in water in the presence of a realistic tetrapropylammonium template under basic conditions. The model corresponds to the synthesis conditions of ZSM5. The free energy profile for the dimer formation ((OH)(3)Si-O-Si-(OH)(2)O(-) or [(OH)(3)Al-O-Si-(OH)(3)](-)) is calculated with ab initio molecular dynamics and thermodynamic integration. The Si-O-Si dimer formation occurs in a two-step manner with an overall free energy barrier of 75 kJ mol(-1). The first step is associated with the Si-O bond formation and results in an intermediate with a five-coordinated Si, and the second one concerns the removal of the water molecule. The template is displaced away from the Si centres upon dimer formation, and a shell of water molecules is inserted between the silicate and the template. The main effect of the template is to slow down the backward hydrolysis reaction with respect to the condensation one. The Al-O-Si dimer formation first requires the formation of a metastable precursor state by proton transfer from Si(OH)(4) to Al(OH)(4)(-) mediated by a solvent molecule. It then proceeds through a single step with an overall barrier of 70 kJ mol(-1). The model with water molecules explicitly included is then compared to a simple calculation using an implicit continuum model for the solvent. The results underline the importance of an explicit and dynamical treatment of the water solvent, which plays a key role in assisting the reaction.     

C-H bond activation by a ferric methoxide complex: modeling the rate-determining step in the mechanism of lipoxygenase.

Lipoxygenases are mononuclear non-heme iron enzymes that regio- and stereospecifcally convert 1,4-pentadiene subunit-containing fatty acids into alkyl peroxides. The rate-determining step is generally accepted to be hydrogen atom abstraction from the pentadiene subunit of the substrate by an active ferric hydroxide species to give a ferrous water species and an organic radical. Reported here are the synthesis and characterization of a ferric model complex, [Fe(III)(PY5)(OMe)](OTf)(2), that reacts with organic substrates in a manner similar to the proposed enzymatic mechanism. The ligand PY5 (2,6-bis(bis(2-pyridyl)methoxymethane)pyridine) was developed to simulate the histidine-dominated coordination sphere of mammalian lipoxygenases. The overall monoanionic coordination provided by the endogenous ligands of lipoxygenase confers a strong Lewis acidic character to the active ferric site with an accordingly positive reduction potential. Incorporation of ferrous iron into PY5 and subsequent oxidation yields a stable ferric methoxide species that structurally and chemically resembles the proposed enzymatic ferric hydroxide species. Reactivity with a number of hydrocarbons possessing weak C-H bonds, including a derivative of the enzymatic substrate linoleic acid, scales best with the substrates' bond dissociation energies, rather than pK(a)'s, suggesting a hydrogen atom abstraction mechanism. Thermodynamic analysis of [Fe(III)(PY5)(OMe)](OTf)(2) and the ferrous end-product [Fe(II)(PY5)(MeOH)](OTf)(2) estimates the strength of the O-H bond in the metal bound methanol in the latter to be 83.5 +/- 2.0 kcal mol(-1). The attenuation of this bond relative to free methanol is largely due to the high reduction potential of the ferric site, suggesting that the analogously high reduction potential of the ferric site in LO is what allows the enzyme to perform its unique oxidation chemistry. Comparison of [Fe(III)(PY5)(OMe)](OTf)(2) to other coordination complexes capable of hydrogen atom abstraction shows that, although a strong correlation exists between the thermodynamic driving force of reaction and the rate of reaction, other factors appear to further modulate the reactivity.     

Kinetics and mechanism of the reaction of para‐chlorophenyl aryl chlorophosphates with anilines in acetonitrile

The kinetics and mechanism of the nucleophilic substitution reactions of p‐chlorophenyl aryl chlorophosphates ( 2 ) with anilines are investigated in acetonitrile at 55°C. Relatively large magnitudes of ρ_X and β_X values are indicative of a large degree of bond making in the TS. Smaller magnitudes of ρ_X (0.20 for X = H) and ρ_XY (?0.30) than those for the corresponding reactions with phenyl aryl chlorophosphates ( 1 ) (ρ_X = 0.54 for X = H and ρ_XY = ?1.31) are interpreted to indicate partial electron loss, or shunt, towards the electron acceptor equatorial ligand (p‐ClC₆H₄O‐) in the bipyramidal pentacoordinated transition state. The inverse secondary kinetic isotope effects (k_H/k_D = 0.64–0.87) involving deuterated aniline (ND₂C₆H₄X) nucleophiles, and small ΔH^? and large negative ΔS^? are obtained. These results are consistent with a concerted nucleophilic substitution mechanism. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 632–637, 2002     

Ab initio kinetics of the reaction of HCO with NO: abstraction versus association/elimination mechanism

The kinetics and mechanism for the reaction of HCO with NO occurring by both singlet and triplet electronic state potential-energy surfaces (PESs) have been studied at the modified Gaussian-2 level of theory based on the geometric parameters optimized by the Becke-3 Lee-Yang-Parr/6-311G(d,p) method. There are two major reaction channels on both singlet and triplet PESs studied: one is direct H abstraction producing CO+HNO and the other is association forming a stable HC(O)NO (nitrosoformaldehyde) molecule. The dominant reaction is predicted to be the direct H abstraction occurring primarily by the lowest-energy path via a loose hydrogen-bonding singlet molecular complex, ON...HCO, with a 2.9-kcal/mol binding energy and a small decomposition barrier (1.9 kcal/mol). The commonly assumed HC(O)NO intermediate, predicted to lie below the reactants by 27.7 kcal/mol, has a high HNO-elimination barrier (34.5 kcal/mol). Bimolecular rate constants for the formation of the singlet products and their branching ratios have been calculated in the temperature range of 200-3000 K. The rate constant for the disproportionation process producing HNO+CO, found to be affected strongly by multiple reflections above the well of the complex at low temperature, is predicted to be k(HNO)=3.08 x 10(-12) T(0.10) exp(242T) for 200-500 K, and 1.72 x 10(-16) T(1.47) exp(888T) for 500-3000 K in units of cm(3) molecule(-1) s(-1). The high- and low-pressure rate constants for the association process forming HC(O)NO can be represented by k(infinity)=4.42 x 10(-11) T(0.25) exp(-28T) cm(3) molecule(-1) s(-1) (200-3000 K) and k(0)=7.30x10(-16) T(-5.75) exp(-719T) (200-1000 K) and 1.82 x 10(2) T(-11.92) exp(1846T) (1000-3000 K) cm(6) molecule(-2) s(-1) for N(2)-buffer gas. The absolute values of total rate constant, predicted to be weakly dependent negatively on temperature but positively on pressure, are in close agreement with most experimental data within their reported errors.     

Switch-over in photochemical reaction mechanism from hydrogen abstraction to exciplex-induced quenching: interaction of triplet-excited versus singlet-excited acetone versus cumyloxyl radicals with amines

The fluorescence and phosphorescence quenching of acetone by 13 aliphatic amines has been investigated. The bimolecular rate constants lie in the range of 10(8)-10(9) M(-1) s(-1) for singlet-excited acetone and 10(6)-10(8) M(-1) s(-1) for the triplet case. The rate data indicate that a direct hydrogen abstraction process dominates for triplet acetone, while a charge-transfer mechanism, namely, exciplex-induced quenching, becomes important for singlet-excited acetone. Pronounced stereoelectronic effects toward H abstraction, e.g., for 1,4-diazabicyclo[2.2.2]octane (DABCO), and significant steric hindrance effects, e.g., for N,N-diisopropyl-3-pentylamine, are observed. A negative activation energy (E(a) = -0.9 +/- 0.2 kcal mol(-1) for triethylamine and DABCO) and the absence of a significant solvent effect on the fluorescence quenching of acetone are indicative of the involvement of exciplexes. Full electron transfer can be ruled out on the basis of the low reduction potential of acetone, which was found to lie below -3.0 V versus SCE. The participation of H abstraction for triplet acetone is corroborated by the respective quenching rate constants, which resemble the reaction rate constants for cumyloxyl radicals. The latter were measured for all 13 amines and showed also a dependence on the electron donor properties of the amines. It is suggested that the H abstraction proceeds directly and not through an exciplex or ion pair. Further, abstraction from N-H bonds in addition to alpha C-H bonds has been corroborated as a significant pathway for excited acetone. Product studies and quantum yields for photoreduction of singlet- and triplet-excited acetone by triethylamine (8% for S(1) versus 24% for T(1)) are in line with the suggested mechanisms of quenching through an exciplex and photoreduction through direct H abstraction.     

Rhodium-catalyzed substitution reaction of aryl fluorides with disulfides: p-orientation in the polyarylthiolation of polyfluorobenzenes

In the presence of a catalytic amount of RhH(PPh3)4 and 1,2-bis(diphenylphosphino)benzene, an aromatic fluoride, an organic disulfide (0.5 equiv), and triphenylphosphine (0.5 equiv) reacted in refluxing chlorobenzene to give an aryl sulfide in high yield. Since triphenylphosphine trapped fluoride atoms forming phosphine difluoride, both organothio groups of the disulfide reacted effectively, and the fluoride substituent reacted more readily than the chloride and bromide. The reaction of hexafluorobenzene and a diaryl disulfide gave 1,4-diarylthio-2,3,5,6-tetrafluorobenzene, 1,2,4,5-tetraarylthio-3,6-difluorobenzene, and hexaarylthiobenzene in a stepwise manner; pentafluorobenzene gave 1-arylthio-2,3,5,6-tetrafluorobenzene; 1,2,3,4-tetrafluorobenzene gave 1,2-diarylthio-3,6-difluorobenzene; and 1,2,4,5-tetrafluorobenzene gave 1,4-diarylthio-2-5-difluorobenzene. The polyarylthiolation reaction of polyfluorobenzenes exhibited a strong tendency to form 1,4-difluorobenzenes.     

P(i-BuNCH2CH2)3N: an efficient promoter for the nucleophilic aromatic substitution reaction of aryl fluorides with aryl TBDMS (or TMS) ethers

[reaction: see text]. The nucleophilic aromatic substitution reaction between electron-deficient aryl fluorides and aryl TBDMS (or TMS) ethers has been shown to be efficiently promoted by proazaphosphatranes such as P(i-BuNCH(2)CH(2))(3)N (3). Excellent yields of diaryl ether products were obtained under unusually mild conditions.     

The nature of the monomer insertion step in the allylnickel(II)-catalyzed 1,4-polymerization of 1,3-butadiene: sigma-allyl-insertion mechanism versus pi-allyl-insertion mechanism

We present a theoretical investigation on the nature of the monomer insertion step in the allylnickel(II)-catalyzed 1,4-polymerization of 1,3-butadiene that employed a gradient-corrected DFT method. We have explored critical elementary steps of the whole polymerization cycle for the trans-1,4 regulating cationic allylnickel(II) [RC3H4NiII(C4H6)L]+ catalyst. These steps are i) cis-butadiene insertion into either the eta 1-sigma-butenyl-NiII bond (sigma-allyl insertion mechanism) or the eta 3-pi-butenyl-NiII bond (pi-allyl insertion mechanism) along with competing pathways for generation of trans-1,4 and cis-1,4 polymer units, and ii) anti-syn isomerization. Based on the analysis of geometric and electronic structures of key species involved and the energetics, we present a detailed insight into the different nature of the monomer insertion step according to the two mechanistic alternatives. An understanding of why the pi-allyl insertion mechanism is favored over the sigma-allyl insertion mechanism is provided. eta 1-sigma-butenyl-NiII Species are predicted to be sparsely populated and also distinctly less reactive than eta 3-pi-butenyl-NiII species. Although they are commonly believed to be reactive intermediates, eta 1-sigma-butenyl-NiII species are, therefore, not likely to be involved along viable pathways for cis-butadiene insertion into the butenyl-NiII bond. The present investigation corroborates our previous conclusion that the pi-allyl insertion mechanism represents the preferred mechanism for the monomer insertion step in the allylnickel(II)-catalyzed 1,4-polymerization of 1,3-butadiene. On the other hand, the suggested alternative sigma-allyl insertion mechanism has to be considered to be not operative, for both thermodynamic and kinetic reasons. Furthermore, the sigma-allyl insertion mechanism would neither provide a rationalization of cis-trans selectivity nor of chemoselectivity in the allylnickel(II)-catalyzed 1,4-polymerization of 1,3-butadiene.     

Kinetics and mechanism for the oxidation of alkanes by peroxynitrous acid in the gas phase: the slow step involving reaction with oh radicals

The relative rate constants (kRH/kEtH), the temperature dependence of these constants at from 5 to 55 °C, and the activation parameters were found for reactions of propane, butane, pentane, hexane, isobutane, cyclopentane, and cyclohexane with peroxynitrous acid (HOONO) in water. The similarity of these results to the data for the reaction of alkanes with OH radicals confirms that the active species in the reactions of HOONO with hydrocarbons in water are OH radicals formed in the homolysis of the HO—ONO bond.     

Multiple high-level QM/MM reaction paths demonstrate transition-state stabilization in chorismate mutase: correlation of barrier height with transition-state stabilization

Multiple profiles for the reaction from chorismate to prephenate in the enzyme chorismate mutase calculated with hybrid density functional combined quantum mechanics/molecular mechanics methods (B3LYP/6-31G(d)-CHARMM27) agree well with experiment, and provide direct evidence of transition-state stabilization by this important enzyme, which is at the centre of current debates about the nature of enzyme catalysis.     

Rate and mechanism of the reaction of alkenes with aryl palladium complexes ligated by a bidentate P,P ligand in Heck reactions

The regioselectivity of the Heck reaction is supposed to be highly affected by the electronic properties of the alkene and the ionic or neutral character of the aryl palladium(II) complexes involved in the reaction with alkenes. In Heck reactions performed in dmf, [Pd(dppp){dppp(O)}Ph](+) (dppp=1,2-bis(diphenylphosphino)propane) is generated in the oxidative addition of PhI with [Pd(0)(dppp)(OAc)](-) formed in situ from Pd(OAc)(2) associated to two equivalents of dppp. [Pd(dppp){dppp(O)}Ph](+) is not very reactive with alkenes (styrene or methyl acrylate); however, it reacts with iodide ions (released in the catalytic reactions) to give [Pd(dppp)IPh] and with acetate ions (used as base) to give [Pd(dppp)(OAc)Ph]. [Pd(dppp)(OAc)Ph] reacts with styrene and methyl acrylate exclusively by an ionic mechanism, that is, via the cationic complex [Pd(dppp)(dmf)Ph](+) formed by dissociation of the acetate ion. The reaction of [Pd(dppp)IPh] is more complex and substrate dependent. It reacts with styrene exclusively by the ionic mechanism via [Pd(dppp)(dmf)Ph](+). [Pd(dppp)IPh] (neutral mechanism) and [Pd(dppp)(dmf)Ph](+) (ionic mechanism) react in parallel with methyl acrylate. [Pd(dppp)(dmf)Ph](+) is more reactive than [Pd(dppp)IPh] but is always generated at lower concentration.     

Controlling diastereoselectivity in the reactions of enantiomerically pure alpha-bromoacyl-imidazolidinones with nitrogen nucleophiles: substitution reactions with retention or inversion of configuration

Diastereoselective substitution reactions of [small alpha]-bromoacyl-imidazolidinones with nitrogen nucleophiles can be promoted with either retention or inversion of configuration by carrying out reactions under epimerising or non-epimerising conditions.     

CuI-catalyzed coupling reaction of beta-amino acids or esters with aryl halides at temperature lower than that employed in the normal Ullmann reaction. Facile synthesis of SB-214857

[reaction: see text] The CuI-catalyzed coupling reaction of aryl halides with beta-amino acids or beta-amino esters is completed at 100 degrees C in 48 h, which indicates that the structure of the beta-amino acid has an accelerating effect for the Ullmann-type aryl amination reaction. This coupling reaction can be used to prepare enantiopure N-aryl beta-amino acids. An efficient synthetic route to SB214857, a potent GPIIb/IIIa receptor antagonist, is developed using this method.     

An unexpected course of the Meisenheimer reaction : aryl phosphates in the reaction of phosphoryl chloride with 2, 3-diphenylquinoxaline-N1-oxide.

Contrary to what is observed with other π-deficient heteroaromatic N-oxides, the reaction of 2, 3-diphenylquinoxaline-N₁-oxide with OPCl₃ gives only very poor yields of chlorinated quinoxalines. It is shown that the major product arises from an unprecedented attack by the nucleophilic oxygen atom of the reagent at a carbon atom of the homocycle of the O-phosphorylated N-oxide, leading ultimately to the corresponding mono- (or di-) aryl ester of phosphoric acid. Using a much smaller excess of OPCl₃ and dilution of the medium with an inert solvent strongly increase the yield of chlorination products.