INTERMOLECULAR ISOTOPE EFFECT

Intermolecular isotope effects upon ion abundances are, in general, not reliable guides as to intermolecular kinetic isotope effects. Intermolecular kinetic isotope effects kl(E)/ku(E) could be determined by PIPECO, although few measurements have been reported [210]. It would be necessary to conduct measurements at two different photon energies since, in general, the molecules Mj and Mn would not have the same ionization energies (IEs). In this way, the molecular ions Mj" and M could be formed with the same internal energy (E = hv — IE). 

The intramolecular isotope effect /H //D (in the El mass spectrum) on the loss of a hydrogen atom from the monodeuteroacetylene ion has been found to be 1.9. The corresponding intermolecular isotope effect was 1.16 (i.e. C2H2 vs. C2D2) [356]. This figure compares with a value of 3.3 reported in an earlier study [221] for the same isotope effect. Intermolecular isotope effects on loss of a hydrogen atom from metastable... 

To digress, the method of internal reference is a device for making interpretation of intermolecular isotope effects on ion abundances more sound, even if not watertight. What is done is to use as an internal reference a reaction whose rate coefficient, kREF(E), is not expected to be affected by the isotope substitution. The product abundance for the isotopic reaction of interest in each molecule is divided by the product abundance for the reference reaction in that molecule (intramolecular comparison). These normalised abundances for the different molecules are then compared to give the isotope effects (intermolecular comparison). 

Studies of the molar volumes of perdeuteriated organic compounds might be expected to be informative about non-bonded intermolecular forces and their manifestations, and such studies might be considered to obviate the necessity of investigating steric isotope effects in reacting systems. The results from non-reacting systems could then be simply applied to the initial and transition states in order to account for a kinetic steric isotope effect. 

The intramolecular and intermolecular deuterium isotope effects in the cycloaddition of acrylonitrile to allene (equation 98) have been studied by Dolbier and Dai231,232. The intramolecular KIEs in the allene-acrylonitrile system were found to be 1.21 0.02 at 206°C and 1.14 0.02 at 225°C. A negligible intermolecular SKIE was found in the reaction of the mixture of tetradeuteriated and undeuteriated allene using a limited amount of acrylonitrile (ku/ku) = 1.04 0.05 at 190-210 °C for D0/D4 allene. An equilibrium deuterium IE of 0.92 0.01 was found at 280-287 5°C (15-45 h reaction time). 

Song and Beak161 have used intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects to investigate the mechanism of the tin tetrachloride catalysed ene-carbonyl enophile addition reaction between diethyloxomalonate and methylenecy-clohexane (equation 105). These ene reactions with carbonyl enophiles can occur by a concerted (equation 106) or a stepwise mechanism (equation 107), where the formation of the intermediate is either fast and reversible and the second step is slow k- > k-i), or where the formation of the intermediate (the k step) is rate-determining. 

Song and Beak found intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects of 1.1 0.2 and 1.2 0.1, respectively, for the tin tetrachloride catalysed ene reaction. Since significant intramolecular and intermolecular primary deuterium kinetic isotope effects of between two and three have been found for other concerted ene addition reactions161, the tin-catalysed reaction must proceed by the stepwise pathway with the k rate determining step (equation 107). 

The isotope effects have been interpreted in terms of a mechanism involving two equilibrating zwitterionic intermediates (equation 110). In this instance, the k step is partially reversible and both the intermolecular and intramolecular isotope effects are a composite of the isotope effects in several steps (Schemes 26 and 27). 

In the mechanism study of /V-benzyl-/V -alkyl hydroxylamines, regarding oxidation with HgO and p-benzoquinone, it has been proposed on the basis of intra- and intermolecular kinetic isotope effects that, initially, there takes place a one-electron transfer from a nitrogen atom to the oxidant, with a subsequent proton abstraction (106—108). 

Wolfsberg, M. Isotope effects on intermolecular interactions and isotopic vapor pressure differences. J. Chemie Physique 60, 15-22 (1963)... 

Schneider, F.W. and Rabinovitch, B. S., The unimolecular isomerization of methyl-d3 isocyanide. Statistical-weight inverse secondary intermolecular kinetic isotope effects in nonequilibrium thermal systems. J. Am. Chem. Soc. 85, 2365 (1963). 

Any effect exerted by the introduction of isotopes are termed isotope effects. Isotope effects can be intermolecular, e.g., upon D loss from CD4 versus H loss from CH4, or intramolecular, e.g., upon H loss versus D loss from CH2D2. ... 

The O—H N hydrogen bond in the phenylazoresorcinol monoanion is strong, giving a large and positive value of A[S( H) — 8( H)], characteristic of a double minimum potential (Hibbert and Phillips, 1989). Two examples of intermolecularly hydrogen-bonded species for which the isotope effect on the chemical shift has been measured are also given in Table 5. 

Laser flash photolysis of phenylchlorodiazirine was used to measure the absolute rate constants for intermolecular insertion of phenylchlorocarbene into CH bonds of a variety of co-reactants. Selective stabilization of the carbene ground state by r-complexation to benzene was proposed to explain the slower insertions observed in this solvent in comparison with those in pentane. Insertion into the secondary CH bond of cyclohexane showed a primary kinetic isotope effect k ikY) of 3.8. l-Hydroxymethyl-9-fluorenylidene (79), generated by photolysis of the corresponding diazo compound, gave aldehyde (80) in benzene or acetonitrile via intramolecular H-transfer. In methanol, the major product was the ether, formed by insertion of the carbene into the MeO-H bond, and the aldehyde (80) was formed in minor amounts through H-transfer from the triplet carbene to give a triplet diradical which can relax to the enol. 

To discern the ion-radical nature of reactions, the so-called intramolecular and intermolecular proton/deuterium isotope effects may be of use. Baciocchi et al. (2005) revealed ion-radical mechanism for A-demethylation of A,A-dimethylanilines, (CH3)2NAr, by phthalimide-A-oxyl radical (Scheme 4.14). In this reaction, ( e/ D)intra values were derived for reactivity of (CD3)(CH3)NAr, whereas ( H/ D)inter was referred for the reactivity of (CD3)2NAr. The values of (A e/ D)intra were found to be always different and higher than These results, although are incompat-... 

An isotope effect (either kinetic or equihbrium) resulting from reactions in which the different isotopes occupy chemically equivalent alternative reactive sites within the same molecular entity. In such cases, isotopicaUy distinct products are formed. See Intermolecular Isotope Effect Kinetic Isotope Effect Equilibrium Isotope Effect lUPAC (1979) Pure and Appl. Chem. 51, 1725. 

Attempts to use intermolecular and intramolecular kinetic isotope effects (KIE s) to identify a complexation step during ortholithiation have so far been inconclusive. Both intramolecular and intermolecular KIE s for the deprotonation of 2 and 3 by s-BuLi... 

The intramolecular kinetic isotope effect determined in reaction of BTNO with p-MeO-C6H4CH(D)0H gave a h/ d ratio of 5.6 in MeCN , consistent with a rate-determining H-abstraction step. Additional determinations gave a h/ d of 7 with PhCH(D)OH, and 12 for the intermolecular competition of fluorene vs. 9,9-dideuteriofluorene. The latter value supports the contribution of tunnelling already commented on for reaction of PINO with various C—H donors ( h/ d values in the 11-27 range) . ... 

Intermolecular reactions of propargylic alcohols with a-methylstyrene gave the corresponding 1-hexene-5-ynes in moderate yields with complete regioselectivity (Scheme 7.30). The incorporation of a deuterium atom at the C-6 position (acetylenic terminal carbon) of the product and a substantial isotope effect (kH/fco = 4) were observed when a-methylstyrene-methyl-dj was used in place of a-methylstyrene. It is considered that the Cp-Cy double bond of an allenylidene complex reacts with a-methylstyrene, where the allenylidene complex works as an enophile, to afford the corresponding vinylidene complex via an allenylidene-ene reaction, as shown in Scheme 7.30. 

The intermolecular kinetic isotope effect for the competition of 20 with its deuteriated analogue 22 in chloroform was negligible (Scheme 10, h/ d = 1-00 0.02). Like in other trisubstituted alkenes, this result was interpreted in terms of irreversible formation of a perepoxide intermediate. 

SCHEME 10. Intermolecular isotope effects in the photooxygenation of alkenes 20 vs 22... 

Many mechanisms had been proposed in the past to rationalize this selectivity (tri-oxanes, perepoxide, exciplex, dipolar or biradical intermediates) however, it is now generally accepted that the reaction proceeds through an intermediate exciplex which has the structural requirements of a perepoxide. This assumption is supported by (a) the lack of stereoselectivity in the reactions with chiral oxazolines and tiglic acid esters (b) the comparison of the diastereoselectivity of dialkyl substituted acrylic esters with structurally similar non-functionalized aUtenes (c) the intermolecular isotope effects in the photooxygenation of methyl tiglate and (d) the solvent effects on regioselectivity. ... 

SCHEME 44. Intermolecular kinetic isotope effect in the intrazeolite photooxygenation of 1-phenyl-3 -methyl- 2-butene... 

A negligible intermolecular isotope effect of %/ d = 1.03 0.02 indicated that also for trisubstituted alkenes, formation of a perepoxide-type transition state is the ratedetermining step. 

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