Eliminations from (E)-O-Arylbenzaldoximes promoted by tertiary amines in acetonitrile. Effects of aryl substituents, base strength, and leaving group upon the nitrile-forming transition state

1988 ◽  
Vol 110 (18) ◽  
pp. 6145-6148 ◽  
Author(s):  
Bong Rae. Cho ◽  
Kee Dong. Kim ◽  
Jong Chan. Lee ◽  
Nam Soon. Cho
Keyword(s):  
Transition State ◽  
Tertiary Amines ◽  
Leaving Group ◽  
Base Strength

Effect of Medium on Reactivity for Alkaline Hydrolysis of p-Nitrophenyl Acetate and S-p-Nitrophenyl Thioacetate in DMSO-H2O Mixtures of Varying Compositions: Ground State and Transition State Contributions

2021 ◽  
Author(s):  
Ik-Hwan Um ◽  
Seungjae Kim
Keyword(s):  
Transition State ◽  
Alkaline Hydrolysis ◽  
Ground State ◽  
Rate Constants ◽  
Kinetic Data ◽  
Reaction Medium ◽  
Stepwise Mechanism ◽  
Rate Determining Step ◽  
Leaving Group ◽  
Hydrolysis Of

Second-order rate constants (kN) for reactions of p-nitrophenyl acetate (1) and S-p-nitrophenyl thioacetate (2) with OH‒ have been measured spectrophotometrically in DMSO-H2O mixtures of varying compositions at 25.0 ± 0.1 oC. The kN value increases from 11.6 to 32,800 M‒1s‒1 for the reactions of 1 and from 5.90 to 190,000 M‒1s‒1 for those of 2 as the reaction medium changes from H2O to 80 mol % DMSO, indicating that the effect of medium on reactivity is more remarkable for the reactions of 2 than for those of 1. Although 2 possesses a better leaving group than 1, the former is less reactive than the latter by a factor of 2 in H2O. This implies that expulsion of the leaving group is not advanced in the rate-determining transition state (TS), i.e., the reactions of 1 and 2 with OH‒ proceed through a stepwise mechanism, in which expulsion of the leaving group from the addition intermediate occurs after the rate-determining step (RDS). Addition of DMSO to H2O would destabilize OH‒ through electronic repulsion between the anion and the negative-dipole end in DMSO. However, destabilization of OH‒ in the ground state (GS) is not solely responsible for the remarkably enhanced reactivity upon addition of DMSO to the medium. The effect of medium on reactivity has been dissected into the GS and TS contributions through combination of the kinetic data with the transfer enthalpies (ΔΔHtr) from H2O to DMSO-H2O mixtures for OH‒ ion.

scholarly journals Inverse enzyme isotope effects in human purine nucleoside phosphorylase with heavy asparagine labels

2018 ◽  
Vol 115 (27) ◽  
pp. E6209-E6216 ◽  
Author(s):  
Rajesh K. Harijan ◽  
Ioanna Zoi ◽  
Dimitri Antoniou ◽  
Steven D. Schwartz ◽  
Vern L. Schramm
Keyword(s):  
Transition State ◽  
Purine Nucleoside Phosphorylase ◽  
Isotope Effects ◽  
Catalytic Site ◽  
Path Sampling ◽  
Transition Path ◽  
Transition Path Sampling ◽  
Steady State Kinetics ◽  
Leaving Group ◽  
Transition State Barrier

Transition path-sampling calculations with several enzymes have indicated that local catalytic site femtosecond motions are linked to transition state barrier crossing. Experimentally, femtosecond motions can be perturbed by labeling the protein with amino acids containing 13C, 15N, and nonexchangeable 2H. A slowed chemical step at the catalytic site with variable effects on steady-state kinetics is usually observed for heavy enzymes. Heavy human purine nucleoside phosphorylase (PNP) is slowed significantly (kchemlight/kchemheavy = 1.36). An asparagine (Asn243) at the catalytic site is involved in purine leaving-group activation in the PNP catalytic mechanism. In a PNP produced with isotopically heavy asparagines, the chemical step is faster (kchemlight/kchemheavy = 0.78). When all amino acids in PNP are heavy except for the asparagines, the chemical step is also faster (kchemlight/kchemheavy = 0.71). Substrate-trapping experiments provided independent confirmation of improved catalysis in these constructs. Transition path-sampling analysis of these partially labeled PNPs indicate altered femtosecond catalytic site motions with improved Asn243 interactions to the purine leaving group. Altered transition state barrier recrossing has been proposed as an explanation for heavy-PNP isotope effects but is incompatible with these isotope effects. Rate-limiting product release governs steady-state kinetics in this enzyme, and kinetic constants were unaffected in the labeled PNPs. The study suggests that mass-constrained femtosecond motions at the catalytic site of PNP can improve transition state barrier crossing by more frequent sampling of essential catalytic site contacts.

Ligand Substitution Reactions

2007 ◽  
Author(s):  
Robert B. Jordan
Keyword(s):  
Transition State ◽  
Coordination Number ◽  
Reaction Rate ◽  
Ligand Substitution ◽  
Substitution Reactions ◽  
Definite Evidence ◽  
Oxidation Reduction ◽  
Leaving Group ◽  
Group 2 ◽  
Ligand Substitution Reactions

In ligand substitution reactions, one or more ligands around a metal ion are replaced by other ligands. In many ways, all inorganic reactions can be classified as either substitution or oxidation-reduction reactions, so that substitution reactions represent a major type of inorganic process. Some examples of substitution reactions follow: The operational approach was first expounded in 1965 in a monograph by Langford and Gray. It is an attempt to classify reaction mechanisms in relation to the type of information that kinetic studies of various types can provide. It delineates what can be said about the mechanism on the basis of the observations from certain types of experiments. The mechanism is classified by two properties, its stoichiometric character and its intimate character. The Stoichiometric mechanism can be determined from the kinetic behavior of one system. The classifications are as follows: 1. Dissociative (D): an intermediate of lower coordination number than the reactant can be identified. 2. Associative (A): an intermediate of larger coordination number than the reactant can be identified. 3. Interchange (I): no detectable intermediate can be found. The intimate mechanism can be determined from a series of experiments in which the nature of the reactants is changed in a systematic way. The classifications are as follows: 1. Dissociative activation (d): the reaction rate is more sensitive to changes in the leaving group. 2. Associative activation (a): the reaction rate is more sensitive to changes in the entering group. This terminology has largely replaced the SN1, SN2 and so on type of nomenclature that is still used in physical organic chemistry. These terminologies are compared and further explained as follows: Dissociative [D = SN1 (limiting)]: there is definite evidence of an intermediate of reduced coordination number. The bond between the metal and the leaving group has been completely broken in the transition state without any bond making to the entering group. Dissociative interchange (1d= SN1): there is no definite evidence of an intermediate. In the transition state, there is a large degree of bond breaking to the leaving group and a small amount of bond making to the entering group.

Ambident Heterocyclic Reactivity: Alkylation of 4-Substituted and 2,4-Disubstituted Benzimidazoles

1994 ◽  
Vol 47 (8) ◽  
pp. 1523 ◽  
Author(s):  
MR Haque ◽  
M Rasmussen
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Electrostatic Field ◽  
Transition States ◽  
Alkyl Halides ◽  
Methyl Group ◽  
Site Selectivity ◽  
Leaving Group ◽  
Standard Set ◽  
Specific Association

The N1/N3-alkylation patterns of 4-amino-, 4-methyl- and 4-nitro-benzimidazole anions, and their 2-methyl analogues, with a standard set of primary alkyl halides (in dimethylformamide, 30°) have been determined and compared. The observed regioselectivities are dominated by proximal effects-electrostatic field, non-bonded steric and in some cases specific association (hydrogen bonding)-the interplay of which is critically dependent on the (variable) geometries of the SN2 transition states involved, in particular on the N---C distance of the developing N-alkyl bonds. The presence of a symmetrically placed 2-methyl group produces an enhanced N1/N3 site selectivity, very sensitive to the loose-tight nature of the transition state. Halide leaving group effects on butylation regioselectivities of 2-unsubstituted, 2-ethoxy-, 2-methyl- and 2-chloro-4-methylbenzimidazole anions, whilst small, are consistent with a Bell-Evans-Polanyi analysis of SN2 transition state variations, with the earlier transition states of CH3(CH2)3I leading to reduced regioselectivities.

Solvent effects on the structure of SN2 transition states

1978 ◽  
Vol 56 (20) ◽  
pp. 2691-2699 ◽  
Author(s):  
Kenneth Charles Westaway
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Solvent Effects ◽  
Kinetic Isotope Effect ◽  
Transition States ◽  
State Structure ◽  
Transition State Structure ◽  
Kinetic Isotope ◽  
Wide Range ◽  
Leaving Group

Two research groups have used heavy atom leaving group kinetic isotope effects to determine how the structure of an SN2 transition state is affected by a change in solvent. Two completely different types of behaviour were observed in these studies. In one case, the leaving group kinetic isotope effect, and thus the transition state structure, changed markedly when the solvent was varied over a reasonably narrow range. In the other study, the leaving group kinetic isotope effect (transition state structure) remained constant over a wide range of solvents. A model describing the interaction between solvent molecules and SN2 transition states is developed and a SolvationruleforSN2reactions which rationalizes the different experimental results is explained and justified. Finally, predictions based on the solvation rule are shown to be in agreement with the results of theoretical calculations of solvent effects on SN2 transition states and secondary α deuterium kinetic isotope effect measurements.

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