C Isotope Effects

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

The C isotope effects for the Cope elimination (17-8) show that both the C—H and C—N bonds have been extensively broken in the transition state. 

Fig. 12.1 (continued) (c) Isotope effects on mean square amplitudes (upper curve) and root mean square amplitudes (lower curve) as a function of temperature for hypothetical nondissociating molecules. At low temperatures the molecules are in the ground state and the amplitude is nearly independent of temperature. At higher temperature the vibrational amplitudes increase due to excitation into upper levels (Fig. 12.1) but the ratios drop smoothly to the classical value of unity at very high temperature (Fig. 12.1)... 

Kinetic studies were made on the cleavage of franx-cinnamate to benzoic acid by stoich. [Ru0 p7aq. 1.7M NaOH/85°C isotope effects and activation parameters were determined. Formation of an alkene-[RuO ] cyclic Ru(lV) ester (1), oxidation of this with more ruthenate to the cyclic Ru(Vl) ester (2) and oxidative decomposition of this via (3) to aldehydes R CHO and R CHO was suggested. The aldehydes are subsequently oxidised to R COOH and R COOH by more [RuO ] (not shown in the Scheme) (Fig. 1.16) [349, 350],... 

The predictive capabilities of results of theoretical calculations of isotope effects have again been questioned,94 following an experimental and theoretical study of the decarboxylation of 3-carboxybenzisoxazole at room temperature (Kemp s reaction). The experimentally determined 15N isotope effect in acetone is 1.0312 0.0006 and the 13 C isotope effect (1.0448, 1.0445, 1.0472, and 1.0418 in 1,4-dioxane, acetonitrile, DMF, and water, respectively) is independent of solvent polarity even though the reaction rate is markedly solvent dependent. Theoretical models at the semiempirical (AMI, PM3, SAMI) and ab initio (up to B3LYP/6-31+ + G ) levels were all unable to predict the experimental results quantitatively. 

Fig. 7.9 Differential thermal analysis (DTA) under N2 flow of C7ffD38 and C FL. The former molecule shows an endothermal decomposition peak at 416°C while the latter reaches the decomposition peak at much lower temperature 344°C. Isotope effect can be advocated for the explanation of the better stability of the perdeuterated C70 in comparison to its hydrogenated analogous...

Singleton, D. A. Hang, C. Isotope effects and the experimental transition state for a prototypical thermal ene reaction, Tetrahedron Lett. 1999, 40, 8939-8943. 

The intermolecular C-isotope effect for sodium trichloroacetate decarboxylation is reported to be kyjk = 1.0338+0.0007 in water at 70.4 °C, where the rate coefficients correspond to reactions (14) and (15) ... 

The C-isotope effects for malonate anion in quinoline according to reactions (16), (17) and (18) were determined as a function of temperature The... 

Chemical studies also support the indicated mechanism. For example, the p-oxoacid intermediate formed in step h of Eq. 13-48 or Fig. 13-12 has been identified as a product released from the enzyme by acid denaturation during steady-state tumover. Isotopic exchange with in the solvent and measurement of C isotope effects have provided additional verification of the mechanism. TTie catalytic activity of the enzyme is determined by ionizable groups with piC values of 7.1 and 8.3 in the ES com-plex. ... 

Nevertheless, although nitrenes undoubtedly can exist under conditions where rearrangement can occur, the observation of C-isotope effects on rates and products for photochemical as well as for thermal rearrangements and the small effect of solvent in altering... 

Similarly, with malic enzyme, sucrose or glycerol caused a decrease in the K for malate and a slight increase in V (76), with the result that VIK was greatly increased (by a factor of 2 with sucrose and a factor of 5 with glycerol). These changes decreased the C isotope effect on decarboxylation, presumably as the result of changes in the commitments in the system (see Section VII,B below). 

In describing isotope effects, we shall use the notation of Northrop (97), where leading superscripts identify the isotopic atom, with D, T, 13, 14, 15, 17, and 18 standing for deuterium, tritium, C, C, N, O, and 0. The isotope effect is the ratio of parameters for unlabeled and labeled species. Thus V is a deuterium isotope effect on V (i.e., Vh/Vd), and (V/K) is a C isotope effect on V/K. The same notation is used for equilibrium isotope effects, with Afeq being an N isotope effect on Afeq (i-e., Afeq >N/Afeq on). 

As noted above in Section VII,B,3, when a deuterium and C isotope effect are on the same step in the mechanism, deuteration reduces commitments and thus enhances the size of the observed C isotope effect. For a stepwise mechanism, however, deuteration makes a step other than the C-sensitive one more rate limiting, and thus decreases the size of the observed C isotope effect. The C isotope effect with deuterated and unlabeled substrates and the deuterium isotope itself are now no longer independent, but are related by the following equations. 

TABLE IX. C and C Isotope Effects in the Decarboxylation of Monobasic Adds. 

Figure 7 shows an intercomparison of the experimental data on the C isotope effect in intermolecular decarboxylation reactions with theoretical calculations based on the simple model... 

At one time some workers gave serious consideration to the h3qx)thesis that the C isotope effects in decarboxylation reactions are greater than twice the C ones. A summary of the C /C ratios is given in Table XI. The data in Table XI provide little basis for the h3q>othesis that there are significant isotope dependent factors which have been neglected in Section II. 

C. Isotope Effect Studies with Alkanes and Cycloalkanes. 873... 

In [ C-l-methyl]-dj-l,4-dimethylcyclohexane [59] no isotopic perturbation was observed within experimental error. It was concluded that a C-isotope effect on the degenerate equilibrium (54) in m 1,4-dimethyl-cyclohexane is either too small to be detected or non-existent (Booth and Everett, 1980a). 

Equilibrium C isotope effects in 2,3-dimethyl-2-butyl and 1,2-dimethylcyclopentyl cations... 

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