Isotope rate effect

While no primary isotope rate effect was observed, when the hydrogen at C-2 or the pro-S hydrogen at C-3 of malate was replaced by 2H or 3H distinct secondary isotope effects were seen. Thus, k( H) / k(2H) = 1.09 for both the pro-S and the C-3 hydrogen atoms.57 These findings appeared to support the carbocation... 

This simply explains the occurrence of a primary isotope rate effect, "primary" referring to the fact that the rate determining step involves a bond to the isotopically substituted atom. However, many reactions which show large primary isotope effects do not involve dissociation into free particles but rather are displacement reactions wherein the isotopic atom is abstracted by an attacking agent. Since the isotopic atom is bound both in reactant and product and is bound also in the transition state, how can the occurrence of large isotope effects in such processes be explained ... 

Compute the kinetic isotope rate effect at T = 300 K if the C-H stretch mode observ ed in the infrared has a frequency of 2900cm . Use Equation (19.36) ... 

Brown and McDonald (1966) provided another type of kinetic evidence for these size relationships by determining secondary kinetic isotope effects in reactions of pyridine-4-pyridines with alkyl iodides. For example, the isotopic rate ratio in the reaction between 4-(methyl-d3)-pyridine and methyl iodide at 25-0 C in nitrobenzene solution was determined to be kjyfk = l-OOl, while that in the corresponding reaction with 2,6-(dimethyl-d6)-pyridine was 1-095. (Brown and McDonald (1966) estimate an uncertainty of 1% in the k jk values.) Furthermore, the isotopic rate ratio in the case of the 2-(methyl-d3)-compound increased from 1 030 to 1-073 as the alkyl group in the alkyl iodide was changed from methyl to isopropyl, i.e. the isotope effect increased with increasing steric requirements of the alkyl iodide. 

The molecules most profitably studied in connection with purely steric isotope effects have been isotopically substituted biphenyl derivatives. Mislow et al. (1964) reported the first more or less clearcut example of this kind in the isotope effect in the configurational inversion of optically active 9,10-dihydro-4,5-dimethylphenanthrene (7), for which an isotopic rate ratio ( d/ h) of 1-17 at 295-2°K in benzene solution was determined. The detailed conformation of the transition state is not certain in this case, as it involves the mutual passage of two methyl groups, and thus it is difficult to compare the experimental results with... 

In the case of the hydrogen isotopes the effect can be a very serious limitation on their usefulness as tracers since rate differences up to tenfold have been observed for deuterium and of course much higher differences are possible for tritium. There will be some indication of how this limitation operates in the final section of this review. 

The use of the isotope effect to study rate-determining steps in a sequence of chemical reactions represents an additional advantage of radiotracer methodology. The term isotope effect (to be discussed more fully later) refers to the influence on a reaction rate of the difference in the masses of isotopes. This effect may create significant problems in the use of radioisotopes as tracers but can, nevertheless, be used to advantage in a limited number of cases in order to understand the kinetics of certain chemical reactions. 

Distribution Functions and Hydrogen-Deuterium Isotope Effects in Nonthermal Activation Systems. In Sec. II-D, hydrogen-deuterium isotopic rate ratios for monoenergetic systems were discussed. In practice, the measured effects are ratios modified by the energy distribution functions and should be compared to kan/kaD rather than to k,n/ktn. A s appropriate for the system under investigation, one of eqs. (19)-(22) is written for each of the isotopic species and a ratio, kttn/kaD, is thus constructed for comparison of isotope effects. These need not be listed in detail. It should be noted that the distribution function for the normal and isotopically substituted systems will usually be somewhat different (Fig. SB). 

As interesting as these special "exit-channel" effects are in their own right, it has been shown that because of a cancellation, they have no bearing on the MIF phenomenon [15]. We stress this point, since occasionally it is assumed in the literature that the special exit channel effect in the ratios is a key to understanding the MIF. Instead, the mass-independent effect of "scrambled" systems and the anomalously large mass-dependent effect for reactions of the type Q -F OO QOO QOO and QO -F O, have very different origins and are unrelated. Perhaps these remarks may seem paradoxical. The various rate constants for these "isotopically unscrambled" reactions can be used to compute the observables for the isotopically scrambled system, and so compute and 5 0. However, the detailed analysis [15] showed that there is much cancellation, summarized below, and that the theoretical expression for the MIF conditions is now simpler than would appear from fhe expression for the MIF in terms of the individual rate constants [15]. In particular, the zero-point energy effect, important for the individual isotope rate constants, disappears when the combination of them that determines the MIF is calculated. 

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