The effect of the nature of the amine leaving group on the nature of the E2 transition state for the reaction of 1-phenylethylammonium ions with sodium ethoxide in ethanol

1989 ◽  
Vol 67 (9) ◽  
pp. 1457-1467 ◽  
Author(s):  
Peter James Smith ◽  
Md. Amin
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Isotope Effects ◽  
Sodium Ethoxide ◽  
Elimination Process ◽  
Leaving Group ◽  
Hydrogen Deuterium ◽  
Mechanism Transition ◽  
Leaving Groups ◽  
Leaving Group Ability

To investigate the effect of the leaving group on the elimination reaction of 1-phenylethylammonium ions with sodium ethoxide in ethanol at 60 °C, the reaction of seven different quaternary ammonium salts and their β-deuterated analogues with trimethylamine, N-methylpiperidine, N-methyldiethylamine, triethylamine, N,N-dimethylbenzylamine, tripropylamine, and N,N-diethylbenzylamine as leaving groups has been studied. In all cases the elimination, which was shown to proceed via the concerted E2 process, was accompanied by competing substitution reactions. Although a significant dependence of the rate of the elimination process on the nature of the leaving group was noted, there was not any linear correlation with the basicity of the amine leaving group. The primary hydrogen–deuterium kinetic isotope effect for the elimination process, (kH/kD)E, was found to increase initially with an increase of reaction rate, [Formula: see text] for substrates containing the leaving groups trimethylamine, N-methylpiperidine, N-methyldiethylamine, triethylamine, and N,N-dimethylbenzylamine; i.e., (kH/kD)E = 5.03, 5.26, 5.40, 5.83, and 5.85, respectively. A further increase in rate, using substrates with tripropylamine and N,N-diethylbenzylamine as leaving groups resulted in a decrease of the magnitude of the hydrogen–deuterium isotope effect; i. e., (kH/kD)E = 5.42 and 4.67, respectively. It is concluded that steric effects mainly determine leaving group ability. As well, it is concluded that the leaving group ability of the amine determines the structure of the E2 transition state. For the reaction of the poorer leaving groups, trimethylamine, N-methylpiperidine, and N-methyldiethylamine, the proton is morethan one-half transferred at the transition state while for reaction involving the two best leaving groups, tripropylamine and N,N-diethylbenzylamine, the Cβ—H bond is lessthan one-half broken at the transition state. The conclusions are considered in the light of the More O'Ferrall – Jencks potential energy surface diagram. Keywords: elimination mechanism, transition state, isotope effects, leaving group, quaternary salts.

Isotope Effect Studies on Elimination Reactions. XI. The Nature of the Transition State for the E2 Reaction of 2-Phenylethyldimethylanilinium Salts Containing Substituents in the Aniline Ring with Sodium Ethoxide in Ethanol

1975 ◽  
Vol 53 (23) ◽  
pp. 3513-3525 ◽  
Author(s):  
Peter Schmid ◽  
Arthur Newcombe Bourns
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Structural Changes ◽  
Isotope Effects ◽  
Sodium Ethoxide ◽  
Nitrogen Isotope ◽  
Structural Variations ◽  
Hydrogen Deuterium ◽  
Elimination Reactions ◽  
Pass Through

Kinetic isotope effects have been determined for the E2 reactions of a series of 2-phenylethyldimethylanilinium salts containing substituents in the aniline ring with sodium ethoxide in ethanol at 40 °C. The nitrogen isotope effect, (k14/k15−1)100, is not very sensitive to substituent changes but appears to increase slightly with increasing electron-withdrawing ability of the substituents, i.e., 1.19 ± 0.07, 1.13 ± 0.06, 1.12 ± 0.08, 1.30 ± 0.07, and 1.32 ± 0.06 for p-OCH3, p-CH3, p-H, p-Cl, and, m-CF3, respectively. The hydrogen–deuterium isotope effects pass through a minimum in the region of the unsubstituted compound and increase both with increasing electron-donating as well as with electron-withdrawing power of the substituents, i.e. kH/kD = 4.70 ± 0.06, 4.61 ± 0.04, 4.51 ± 0.04, 4.53 ± 0.09, 5.00 ± 0.07, and 5.39 ± 0.07 for p-OCH3, p-CH3, p-H, p-Cl, m-CF3, and p-CF3, respectively. The results are discussed in terms of recent theoretical treatments of the effect of structural variations in the reactants on the nature of the transition state of E2 elimination reactions. The conclusion is reached that the transition states in the present reaction series can be characterized as 'central with slight carbanion character' and that the effect of a change in the ability of the leaving group on the structure of the transition state manifests itself mainly in the direction perpendicular to the reaction coordinate. A simple novel hypothesis is formulated which emphasizes the importance of the location of the transition state in a More O'Ferrall-type potential energy diagram in determining its sensitivity to structural changes in the reactants.

Isotope Effect Studies on Elimination Reactions. IX. The Nature of the Transition State for the E2 Reaction of 2-Arylethylammonium Ions with Ethoxide in Ethanol

1974 ◽  
Vol 52 (5) ◽  
pp. 749-760 ◽  
Author(s):  
P. J. Smith ◽  
A. N. Bourns
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Isotope Effects ◽  
Nitrogen Isotope ◽  
Kinetic Isotope Effects ◽  
Ammonium Ions ◽  
Nitrogen Effect ◽  
Kinetic Isotope ◽  
Leaving Group ◽  
Hydrogen Deuterium

Kinetic isotope effects have been determined for the E2 reaction of some 2-arylethyltrimethyl-ammonium ions with ethoxide in ethanol at 40°. The nitrogen effect, (k14/k15 − 1)100, decreased with increasing electron-withdrawing ability of the para substituent; i.e. 1.37, 1.33, 1.14, and 0.88 for p-OCH3, p-H, p-Cl, and p-CF3, respectively. Furthermore, the primary hydrogen–deuterium isotope effects increased for the same substituents, respectively; i.e. kH/kD = 2.64, 3.23, 3.48, and 4.16. A large positive ρ value of 3.66 was found as well as a small secondary α-deuterium effect of 1.02 for p-H. In addition, the nitrogen isotope effect decreased with increasing strength of the abstracting base for the reaction of ethyltrimethylammonium ion; i.e. 1.86 and 1.41 at 60° for reaction with EtO−–EtOH and t-BuO−–t-BuOH, respectively. The results are discussed in terms of recent theoretical treatments of the effect of base, substituents, and nature of the leaving group on the nature of the transition state for an E2 process. The conclusion is reached that any structural change which causes one bond (C—H) to be weakened more at the transition state will have a corresponding effect on the other bond [Formula: see text]

The effect of the leaving group on the nature of the E2 transition state for reaction of 2-aryl-1-phenylethylammonium ions with ethoxide in ethanol

1981 ◽  
Vol 59 (20) ◽  
pp. 3016-3018 ◽  
Author(s):  
Shune-Long Wu ◽  
Peter James Smith
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Deuterium Isotope Effect ◽  
Significant Dependence ◽  
Leaving Group ◽  
Rate Of Reaction ◽  
Hydrogen Deuterium ◽  
Leaving Groups

The reaction of 2-aryl-1-phenylethylammonium salts with ethoxide in ethanol at 40 °C for five different amine leaving groups has been investigated. A significant dependence of the rate of reaction on the basicity of the leaving group was found. The variation of the primary hydrogen–deuterium isotope effect and pKa of the leaving group was not linear and it is concluded that the proton is less than one-half transferred to base at the transition state for reactions involving the best two leaving groups. In support of this conclusion is the observed opposite variation of kH/kD with ring substituents for the various leaving groups, i.e., for N-methylpyrrolidine, kH/kD = 4.58, 4.72, and 5.01 for p-Me, H, and p-Cl, respectively; for N-methylmorpholine, kH/kD = 6.13, 5.73, and 5.50 for p-Me, H, and p-Cl, respectively.

Secondary α hydrogen–deuterium kinetic isotope effects in the syn-elimination reaction of 2-phenylethyldimethylamine oxide

1987 ◽  
Vol 65 (9) ◽  
pp. 2149-2153 ◽  
Author(s):  
Peter James Smith ◽  
Kenneth Charles Westaway
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Isotope Effects ◽  
Thermal Reaction ◽  
Bond Rupture ◽  
Elimination Process ◽  
Kinetic Isotope ◽  
Hydrogen Deuterium ◽  
Relative Transition

The secondary α-deuterium kinetic isotope effect has been measured for the thermal reaction of 2-phenylethyldimethylamine oxide in 90 mol% DMSO–H2O at 60.0 °C. A large secondary α-deuterium isotope effect of 1.158 per α-D was found, which indicates significant [Formula: see text] bond rupture and very little double bond formation at the transition state for this concerted syn-elimination process. The observed large normal value for (kH/kD)α is discussed in terms of the use of secondary α-D isotope effects for the determination of stereochemistry for a concerted elimination process. Various isotope effects found for the syn elimination of the above amine oxide and those for the anti elimination of 2-arylethyltrimethylammonium salts with ethoxide are considered with respect to the relative transition state structures for syn- and anti-elimination reactions.

A Primary Hydrogen-Deuterium Isotope Effect Study on the Carbonyl Elimination Reaction of 9-Fluorenyl Nitrate with Various Bases

1975 ◽  
Vol 53 (2) ◽  
pp. 263-268 ◽  
Author(s):  
Peter James Smith ◽  
Lorraine Marion Noble
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Isotope Effects ◽  
Effect Study ◽  
Elimination Reaction ◽  
Deuterium Isotope Effect ◽  
Nitrogen Bases ◽  
Transition State Geometry ◽  
Hydrogen Deuterium ◽  
Deuterium Isotope Effects

The carbonyl elimination reaction of 9-fluorenyl nitrate with various nitrogen bases in anhydrous ethanol at 0 °C was examined. In all cases fluorenone was formed in 100% yield indicating that there was not any substitution. A reasonable Brønsted plot was obtained for reaction promoted by structurally similar bases with β = 0.84 which suggests a product-like transition state. As well, deviations from the Brønsted plot are discussed. Primary hydrogen-deuterium isotope effects were measured for reaction promoted by 11 different amine bases. A reasonable correlation was obtained for structurally similar bases when a plot of kH/kDvs. pKa was made. The conclusion is reached that when kH/kD reaches a maximum, ∼9.2 at 0 °C, it remains unchanged and hence is a poor measure of transition state geometry. As well, very poor correlations are found when the abstracting base is tertiary which leads to the conclusion that a comparison of kH/kD values is not warranted for structurally different bases.

Isotope Effect Studies on Elimination Reactions. X. The Nature of The Transition State for the ECO2 Reaction of Para- substituted Benzyl Nitrates with Base in 90% by Volume Ethanol–Water

1975 ◽  
Vol 53 (9) ◽  
pp. 1319-1326 ◽  
Author(s):  
Peter James Smith ◽  
Carol Audrey Pollock ◽  
Arthur Newcombe Bourns
Keyword(s):  
Transition State ◽  
Isotope Effect ◽  
Isotope Effects ◽  
Nitrogen Isotope ◽  
Kinetic Isotope Effects ◽  
The Other ◽  
Theoretical Treatment ◽  
Kinetic Isotope ◽  
Hydrogen Deuterium ◽  
Deuterium Isotope Effects

Kinetic isotope effects have been determined for the Eco2 reaction of para-substituted benzyl nitrates with ethoxide in 90 vol.% ethanol–water at 20°. The nitrogen isotope effect, (k14/k15−1)100 decreased with increasing electron-withdrawing ability of the para-substituent; i.e. 2.26, 1.95, 1.60, and 0.84 for p-CH3, p-H, p-CF3, and p-NO2, respectively. Furthermore, the primary hydrogen–deuterium isotope effects increased also for electron-withdrawing substituents; i.e. kH/kD = 5.78, 6.06, 6.40, 6.67, and 7.05 for p-CH3, p-H, p-Br, p-CF3, and p-NO2, respectively. The results are discussed in terms of a recent theoretical treatment dealing with the effect of substituents on the nature of the transition state for a concerted E2 process. The conclusion is reached that any structural change which causes one bond (carbon–hydrogen) to be weakened more at the transition state will have a corresponding effect on the other bond (oxygen–nitrogen).

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.

2,4-Diazapentadienes. II. A Carbanion Cyclization

1972 ◽  
Vol 50 (5) ◽  
pp. 678-689 ◽  
Author(s):  
D. H. Hunter ◽  
S. K. Sim
Keyword(s):  
Isotope Effect ◽  
Solvent Effects ◽  
Isotope Effects ◽  
Substituent Effects ◽  
Deuterium Exchange ◽  
Hydrogen Deuterium Exchange ◽  
Deuterium Isotope Effect ◽  
Potassium Methoxide ◽  
Proton Shift ◽  
Hydrogen Deuterium

The mechanism of the cyclization and 1,3-proton shift of 1,3,5-triaryl-2,4-diaza-1,3-pentadienes (1) catalyzed by phenyllithium and by potassium methoxide–methanol has been studied. On the basis of substituent effects, hydrogen–deuterium exchange, isotope effects, and solvent effects, it was deduced that both the cyclization and prototropy involve a common W-shaped carbanion which rapidly cyclizes. A kinetic deuterium isotope effect of 2 was calculated for protonation of this intermediate carbanion in methanol.

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