Secondary Α-deuterium Kinetic Isotope Effects Research Articles

Secondary Kinetic Isotope Effects in Oxidative Addition of Benzyl Bromide to Dimethylplatinum(II) Complexes

The secondary α-deuterium kinetic isotope effects (KIEs), (kH/kD)α, have been determined, at different temperatures and in solvents having different polarities, for reaction of PhCH2Br/PhCD2Br with the dimethylplatinum(II) complexes [PtMe2(NN)], in which the bidentate NN ligand is bpy (=2,2′-bipyridine) or bu2bpy (=4,4′-di-tert-butyl-2,2′-bipyridine). The values obtained for the secondary α-deuterium KIEs in acetone solution are close to 1 and may be normal or inverse, but much larger values are found for the reactions in benzene. An explanation is presented on the basis of solvent dependence of the degree of looseness of the transition state in the SN2 mechanism.

Secondary α-deuterium kinetic isotope effects in [2+4] cycloaddition of (E)-2-phenylnitroethene to cyclopentadiene

Secondary a-deuterium kinetic isotope effects confirm that (2?4) cycloaddition between (E)-2-phenylni- troethene and cyclopentadiene occurs in concerted manner, on both the pathway leading to 6-endo-phenyl-5-exo-nitro- norbornene and the pathway leading to the corresponding 6- exo-phenyl-5-endo-nitro isomer. According to Hammond terminology the transition states on competitive pathways should be considered in terms of symmetrical early states.

Secondary Kinetic Deuterium Isotope Effects in the Reaction of MeI with Organoplatinum(II) Complexes

Secondary α-deuterium (α-D) kinetic isotope effects (KIEs) have been determined for the reactions of the (diimine)diarylplatinum(II) complexes [Pt(p-MeC6H4)2(NN)] (NN = bipyridine (bpy), 1a; NN = 4...

The Mechanism Study of Free Radical SH2′ Reactions by Leaving Group Effect and Secondary α‐Deuterium Kinetic Isotope Effect

AbstractThe reactions of free radical addition to allylic compounds are believed to proceed the SH2′ mechanism. It is not clear whether the SH2′ mechanism is concerted or stepwise. The leaving group effects and the secondary α‐deuterium kinetic isotope effects in free radical SH2′ reactions have been determined. The leaving group effect, kBr/kCl, is from 1.88 to 14.3. The secondary α‐deuterium kinetic isotope effects, kH/kD, are 1.20 for 2‐methylallyl chloride and 1,1‐d2‐2‐methylallyl chloride and 1.22 for allyl chloride and 1,1‐d2‐allyl chloride. The free radical SH2′ reactions seem to favor the concerted mechanism.

Secondary alpha-deuterium kinetic isotope effects: assumptions simplifying interpretations of mechanisms of solvolyses of secondary alkyl sulfonates.

For solvolyses of 2-propyl and cyclopentyl sulfonates, logarithms of alpha-deuterium kinetic isotope effects (alpha-KIE) correlate linearly with logarithms of nucleophilic solvent assistance (NSA); correlations have the same slopes, but different intercepts, consistent with both solvent and structural effects on alpha-KIEs for heterolysis, further supported by recent theoretical and experimental data. It is argued that alpha- and beta-KIEs cannot yet distinguish between mechanisms proceeding via one or more transition states of similar energies. Structural, solvent, and isotope effects can be rationalized by heterolysis accompanied by NSA.

Mechanism of Thermoanaerobacterium saccharolyticum beta-xylosidase: kinetic studies.

The catalytic mechanism of Thermoanaerobacterium saccharolyticum beta-xylosidase (XynB) from family 39 of glycoside hydrolases has been subjected to a detailed kinetic investigation using a range of substrates. The enzyme exhibits a bell-shaped pH dependence of k(cat)/K(m), reflecting apparent pK(a) values of 4.1 and 6.8. The k(cat) and k(cat)/K(m) values for a series of aryl xylosides have been measured and used to construct two Brønsted plots. The plot of log(k(cat)/K(m)) against the pK(a) of the leaving group reveals a significant correlation (beta(lg) = -0.97, r(2) = 0.94, n = 8), indicating that fission of the glycosidic bond is significantly advanced in the transition state leading to the formation of the xylosyl-enzyme intermediate. The large negative value of the slope indicates that there is relatively little proton donation to the glycosidic oxygen in the transition state. A biphasic, concave-downward plot of log(k(cat)) against pK(a) provides good evidence for a two-step double-displacement mechanism involving a glycosyl-enzyme intermediate. For activated leaving groups (pK(a) < 9), the breakdown of the xylosyl-enzyme intermediate is the rate-determining step, as indicated by the absence of any effect of the pK(a) of the leaving group on log(k(cat)) (beta(lg) approximately 0). However, a strong dependence of the first-order rate constant on the pK(a) value of relatively poor leaving groups (pK(a) > 9) suggests that the xylosylation step is rate-determining for these substrates. Support for the dexylosylation chemical step being rate-determining for activated substrates comes from nucleophilic competition experiments in which addition of dithiothreitol results in an increase in turnover rates. Normal secondary alpha-deuterium kinetic isotope effects ((alpha-D)(V) or (alpha-D)(V/K) = 1.08-1.10) for three different substrates of widely varying pK(a) value (5.15-9.95) have been measured and these reveal that the transition states leading to the formation and breakdown of the intermediate are similar and both steps involve rehybridization of C1 from sp(3) to sp(2). These results are consistent only with "exploded" transition states, in which the saccharide moiety bears considerable positive charge, and the intermediate is a covalent acylal-ester where C1 is sp(3) hybridized.

The nature of the transition state in diarylmethyl cation – nucleophile combination reactions as probed by secondary α-deuterium isotope effects

Transition-state structures for the carbocation–nucleophile combination reactions of (4-substituted-4'- methoxydiphenyl)methyl cations with water, chloride, and bromide ions in acetonitrile–water mixtures have been investigated by measuring the secondary α-deuterium kinetic and equilibrium isotope effects. Rate constants in the combination direction were measured with laser flash photolysis. Equilibrium constants were measured for the water reaction by a comparison method in moderately concentrated sulfuric acid solutions, for the bromide reaction via the observation of reversible combination, and for the chloride reaction from the ratio of the combination rate constant and the rate constant for the ionization of the diarylmethyl chloride product. The fraction of bond making in the transition state has been calculated as the ratio log (kinetic isotope effect):log (equilibrium isotope effect). For the water reaction, there is 50–65% bond making in the transition state; this is also true for cations that are many orders of magnitude less reactive. The same conclusions, 50–65% bond formation in the transition state independent of reactivity, have previously been made in correlations of log kw vs. log KR. Thus, two quite different measures of transition structure provide the same result. The kH:kD values for the halide combinations in 100% acetonitrile are within experimental error of unity. This is consistent with suggestions that these reactions are occurring with diffusional encounter as the rate-limiting step. Addition of water has a dramatic retarding effect on the halide reactions, with rate constants decreasing steadily with increased water content. Small inverse kinetic isotope effects are observed (in 20% acetonitrile:80% water) indicating that carbon—halogen bond formation is rate-limiting. Comparison of the kinetic and equilibrium isotope effects shows ~25 and ~40% bond formation in the transition states for the reactions with bromide and chloride, respectively.Key words: carbocation, isotope effect, transition state, halide.

Deuterium kinetic isotope effects in gas phase SN2 reactions

Rate coefficients and secondary α-deuterium kinetic isotope effects (KIEs) for the nucleophilic substitution (SN2) reactions of Cl− + CH3Br → CH3Cl + Br−, Cl− + CH3I → CH3Cl + I−, Br− + CH3I → CH3Br + I−, and their perdeuterated analogs are remeasured in the gas phase at 300 K. The measurements confirm our previous results [Gronert et al., J. Am. Chem. Soc. 113 (1991) 4009] and substantial inverse KIEs are measured with an improved accuracy: kH/kD = 0.77 (±0.03), 0.84 (±0.01), and 0.76 (±0.01), respectively, for the above systems. Thus, the experimentally observed effect of deuterium substitution in these reactions is considerably more dramatic than predicted previously by transition state theory where KIEs are calculated to be closer to unity. The experimental KIE values for the series of SN2 reactions, F−, Cl−+CH3Br and F−, Cl−, Br−+CH3I are both found to decrease (i.e. become more inverse) with an increase in the transition-state looseness parameter (RTS) for larger halide anions, in contrast to those for lighter methyl halides which show the expected positive correlations with RTS.

An unusually large secondary α-deuterium kinetic isotope effect in hydride ion SN2 reactions

Theoretical calculations at the HF/6-31+G* level suggest the secondary α-deuterium kinetic isotope effects for hydride ion SN2 reactions are much larger than expected for the structure of the transition state. The secondary α-deuterium kinetic isotope effects for the SN2 reactions between sodium borohydride (hydride ion) and para-methyl- and para-chlorobenzyl chlorides are much larger than expected as the theoretical calculations suggest. It appears the secondary α-deuterium isotope effects are larger than expected for the structure of the SN2 transition state because the hydride ion is too small to affect the Cα—H(D) out-of-plane bending vibrations in the transition state.Key words: secondary α-deuterium kinetic isotope effects, SN2, nucleophilic substitution, transition state, substituent effects.

An unusually large secondary α-deuterium kinetic isotope effect in hydride ion S&lt;sub&gt;N&lt;/sub&gt;2 reactions

An unusually large secondary α-deuterium kinetic isotope effect in hydride ion S&lt;sub&gt;N&lt;/sub&gt;2 reactions

Thermal Isomerizations of Substituted Benzyl Isocyanides: Relative Rates Controlled Entirely by Differences in Entropies of Activation

The absolute and relative rates of thermal rearrangments of substituted benzyl isocyanides were obtained at the temperatures between 170 and 230 °C. The relative rates are independent of temperature and exhibit excellent Hammett correlations (ρ+ = −0.24). The temperature studies yielded activation parameters ( and ) and their differential counterparts ( and ). The differential terms were plotted against σ+. The secondary α-deuterium kinetic isotope effects (kD/kH = 1.11) were measured at several temperatures. The rate data can be rationalized with the cyclic TS. The substituent effects on the rates are due to the entropic contributions.

Secondary α-deuterium kinetic isotope effects in the decomposition of simple α-acetoxydialkylnitrosamines: Nitrosiminium ion intermediates

Abstract Secondary α-deuterium kinetic isotope effects for the pH independent decay of two (N-nitrosoalkylamino)methylacetates (4) and two (N-nitrosoalkylamino)propyl acetates (5) have been determined at 52 °C in aqueous solution, ionic strength 1 M. In all cases the isotope effects are kobsdH/kobsdD ∼ 1.1 – 1.2 (per hydrogen). It is concluded that the direction and magnitude of the isotope effects are inconsistent with mechanisms involving rate limiting reaction at the carbonyl group; and, are consistent with the formation of N-nitrosiminium ions in, or prior to, the rate limiting step.

Theoretical investigation of the origin of secondary α-deuterium kinetic isotope effects

Although the secondary α-deuterium kinetic isotope effect upon the degenerate SN2 reaction of chloromethane with chloride anion arises from changes in α-CH stretching force constants, α-substitution by methyl and/or methoxy groups shows this inverse inductive contribution to be approximately constant and reveals that the trend in the isotope effect (calculated by semiempirical molecular orbital theory) is determined by changes in bending force constants, in accord with the conventional view.

High secondary α-deuterium kinetic isotope effect in the acetolysis and formolysis of dideuterioferrocenylmethyl benzoate

Acetolysis and formolysis of dideuterioferrocenylmethyl benzoate exhibit large secondary α-deuterium kinetic isotope effects and an abnormal temperature dependence. In the presence of LiClO4(ca. 0.1 mol dm–3), which prevents the reversion from solvent-separated to contact ion-pairs, kH/kD at 25 °C amount to 1.53 ± 0.02 (acetolysis) and 1.48 ± 0.03 (formolysis). In the presence of LiClO4 the ratios of Arrhenius pre-exponential factors, AH/AD, are significantly less than unity and amount to 0.49 ± 0.01 (acetolysis) and 0.38 ± 0.04 (formolysis). In the absence of LiClO4 the AH/AD ratios are much smaller (0.02 both in acetolysis and formolysis). We suggest that these surprisingly low values result from a change in rate-determining step over the temperature range, from formation of the solvent-separated ion-pair at low temperatures to reaction of the dissociated carbocation with solvent at the highest temperatures. Whether tunnelling plays any role in these solvolyses is discussed.

Isotope effects in nucleophilic substitution reactions. VIII. The effect of the form of the reacting nucleophile on the transition state structure of an SN2 reaction

A spectroscopic investigation indicated that lithium thiophenoxide exists as a contact ion pair complex in dry diglyme whereas the other alkali metal thiophenoxides exist as a solvent-separated ion pair complex in diglyme. The addition of small amounts of water converts the lithium thiophenoxide contact ion pair complex into a solvent-separated ion pair complex. A smaller secondary α-deuterium kinetic isotope effect and a larger Hammett p value are observed when the nucleophile is the contact ion pair complex in the SN2 reaction between n-butyl chloride and thiophenoxide ion in diglyme. This indicates that the transition state for the contact ion pair complex reaction is tighter with a shorter nucleophile–α-carbon bond than the transition state for the solvent-separated ion pair complex reaction. The secondary α-deuterium kinetic isotope effects for the free ion and the solvent-separated ion pair complex reactions between sodium thiophenoxide and n-butyl chloride in DMF suggest that the loosest transition state is found when the nucleophile is the free ion. Key words: transition state, SN2, isotope, deuterium, Hammett ρ.

Acetolysis of ferrocenylmethyl benzoate. High secondary α-deuterium kinetic isotope effect for primary carbon-oxygen cleavage

Secondary α-deuterium kinetic isotope effect ( KIE) in acetolysis of ferrocenyl-1,1-dideuteriomethyl benzoate was determined at 298 K as kH/ kD = 1.50 (22.5% per D). This appears to be one of the largest KIE observed for carbon-oxygen cleavage. The solvolysis exhibits a ‘special salt effect’, and a common ion rate depression effect, indicating the presence of solvent-separated ion pairs and the return to tight pairs. The high value of KIE in acetolysis strongly suggests that the acetolysis is a limiting dissociative process with the carbonium ion transition state, stabilized mainly by conjugation with the π-system. The entropy of activation (−30 J K −1 mol −1) is very similar to those values we previously determined in ethanolyses of ferrocenylmethyl acetate and benzoate (−22 and −25 J K −1 mol −1), where the KIE was only 11.4% per D. In the latter reactions the stabilization of the transition state probably involves some Fe-C exo bond formation. It appears that the mode of stabilization of the ferrocenylmethyl cation depends on the type of solvolysis and on the nature of the media: high KIE is observed in solvents of high ionizing power. Entropies of activation cannot help in distinguishing between the two possible modes of stabilization.

Secondary α-deuterium kinetic isotope effects for addition of phenyl radical to benzyl isocyanides: An evidence of concerted mechanism.

Addition of phenyl radical to benzyl isocyanides gives benzonitrile and benzyl radicals, exhibiting positive Hammett γ = 0.26 and notable secondary α-deuterium kinetic isotope effects. These can be rationalized by concerted bond formation/cleavage occurring with polar transition states(TS).

Kinetic isotope effects involving deuteriated aniline nucleophiles

Primary and secondary α-deuterium kinetic isotope effects are observed with deuteriated aniline nucleophiles in the SN2 reactions of 1-phenylethyl and benzyl benzenesulphonates, providing evidence in support of the four centre transition state mechanism for the former reaction.

Solvent effects on SN2 transition state structure. II: The effect of ion pairing on the solvent effect on transition state structure

Identical secondary α-deuterium kinetic isotope effects (transition state structures) in the SN2 reaction between n-butyl chloride and a free thiophenoxide ion in aprotic and protic solvents confirm the validity of the Solvation Rule for SN2 Reactions. These isotope effects also suggest that hydrogen bonding from the solvent to the developing chloride ion in the SN2 transition state does not have a marked effect on the magnitude of the chlorine (leaving group) kinetic isotope effects. Unlike the free ion reactions, the secondary α-deuterium kinetic isotope effect (transition state structure) for the SN2 reaction between n-butyl chloride and the solvent-separated sodium thiophenoxide ion pair complex is strongly solvent dependent. These completely different responses to a change in solvent are rationalized by an extension to the Solvation Rule for SN2 Reactions. Finally, the loosest transition state in the reactions with the solvent-separated ion pair complex is found in the solvent with the smallest dielectric constant. Keywords: ion pairs, transition state, solvent effects, nucleophilic substitution, isotope effects.

Isotope effects in nucleophilic substitution reactions. VII. The effect of ion pairing on the substituent effects on SN2 transition state structure

The secondary α-deuterium kinetic isotope effects and substituent effect found in the SN2 reactions between a series of para-substituted sodium thiophenoxides and benzyldimethylphenylammonium ion are significantly larger when the reacting nucleophile is a free ion than when it is a solvent-separated ion pair complex. Tighter transition states are found when a poorer nucleophile is used in both the free ion and ion pair reactions. Also, the transition states for all but one substituent are tighter for the reactions with the solvent-separated ion pair complex than with the free ion. Hammett ρ values found by changing the substituent on the nucleophile do not appear to be useful for determining the length of the sulphur–α-carbon bond in the ion pair and free ion transition states. Keywords: Isotope effects, ion pairing, nucleophilic substitution, SN2 reactions, transition states.