Isotope deuterium substitution

Fig. 4.9. DifiBoing zero-point energies ofprotium- and deuterium-substituted molecules as the cause of primary kinetic isotope effects.

The distribution of a-bromoketones formed in the reaction of acetylcyclopentane with bromine was studied as a function of deuterium substitution. On the basis of the data given below, calculate the primaiy kinetic isotope effect for enolization of... 

The work of Melander and Carter (1964) on 2,2 -dibromo-4,4 -di-carboxybiphenyl-6,6 -d2 (1) has been referred to above in the introductory and theoretical sections, where it was pointed out that the availability of two detailed theoretical computations of the inversion barrier (Westheimer and Mayer, 1946, Westheimer, 1947 Hewlett, 1960) made this system especially attractive for the study of steric isotope efifects. Furthermore, in the preferred initial-state conformation the two bromines are probably in van der Waals contact (cf. Hampsoii and Weissberger, 1936 Bastiansen, 1950), and thus initial-state steric effects are unaffected by deuterium substitution in the 6 and 6 positions. The barrier calculations provided two different theoretical values for the non-bonded H Br distance in the transition state which, together with the corresponding H Br potential function, could be inserted in equation (10) to yield values for A AH. For... 

Deuterium isotope effects have been found even where it is certain that the C—H bond does not break at all in the reaction. Such effects are called secondary isotope effectsf" the term primary isotope effect being reserved for the type discussed previously. Secondary isotope effects can be divided into a and P effects. In a P secondary isotope effect, substitution of deuterium for hydrogen p to the position of bond breaking slows the reaction. An example is solvolysis of isopropyl bromide ... 

Deuterium Substitution. The a and P secondary isotope effects affect the rate in various ways (p. 298). The measurement of a secondary isotope effects provides a means of distinguishing between SnI and Sn2 mechanisms, since for Sn2 reactions the values range from 0.95 to 1.06 per a D, while for S l reactions the values are higher. This method is especially good because it provides the minimum of perturbation of the system under study changing from a H to a D hardly affects the reaction, while other probes, such as changing a substituent or the polarity of the solvent, may have a much more complex effect. 

The main difficulty in obtaining the vinyl radical is that the species easily loses the hydrogen atom and is converted into acetylene. Nevertheless, a very low concentration of the radical H2C=CH has been achieved (Shepherd et al., 1988) by vacuum UV photolysis of ethylene frozen in an argon matrix, and a Fourier transform IR study of this intermediate has been carried out. A variety of and deuterium-substituted ethylene parent molecules were used to form various isotopomers of vinyl radical. On the basis of its isotopic behaviour and by comparison with ab initio... 

The oxidation by Cr(VI) of aliphatic hydrocarbons containing a tertiary carbon atom has been studied by several groups of workers. Sager and Bradley showed that oxidation of triethylmethane yields triethylcarbinol as the primary product with a primary kinetic isotope effect of about 1.6 (later corrected by Wiberg and Foster to 3.1) for deuterium substitution at the tertiary C-H bond. Oxidations... 

The effects of deuterium substitution on the rates of a-hydroxylation of NNN have been measured. The results obtained in vitro, with rat liver microsomes, showed only a small deuterium isotope effect of 1.2 for 2 -hydroxylation, whereas a significant effect of 2.4-2.7 was observed for 5 -hydroxylation (33). Analogous results were obtained 2n vivo when the urinary metabolites... 

For the ds-l-chloro-2-fluoroethylene, an a-deuterium isotope effect (one D) of 0.6 ppm is observed, along with a trans-P-deuterium isotope effect of 0.4 ppm. Looking at the /rau.v-l -chloro-2-fluoroethylcnc system, the a-deuterium isotope effect is 0.5 ppm and the c/s-P-isotope effect is 0.2 ppm. For the 1-chloro-l-fluoroethylene system, trans-P-isotope effect is 0.5 ppm, with the ds-(3-isotope effect being 0.4 ppm. From these results, it appears that trans-deuterium substitution transmits its isotope effect better than ds-deuterium substitution, the same trend as is observed in transmission of coupling constants. 

A few examples of f)-20-KIEs are shown in Fig. 10.3. These effects are markedly dependent on geometry. This is clear from the first example. Deuterium substitution at different (1-hydrogen atoms does not lead to the same rate changes for the chloro-solvolysis. That in mind, it is a bit surprising to see that the diphenylethyl derivative shown in the third example does not show much effect upon D-isotope substitution at the P-carbon. 

Inverse isotope effects such as those found in Table IV are associated with a change in hybridization at the site of deuterium substitutions (60). Hence, it is clear from these data that the transition state is symmetrical with respect to hydridization changes at both olefinic carbons when the reaction is carried out in aqueous solutions. However the last four entries in Table IV indicate that for the oxidation of methyl cinnamate in methylene chloride solutions only the iS-carbon has undergone a hybridization change (from sp ... 

In order to assess the validity of such an approach, within the assumptions of the model outlined, we have recently undertaken an examination of deuterium isotope effects on both the radiative and unimolecular dissociation rates. One such case is that of the protonated dimer of acetone in which either the methyl groups, the protonated oxygen, or both, are deuterium substituted. Results for these four systems are shown in Figure 14 and the rate data derived are summarized in Table 1. 

For the Fe-S proteins, the frequencies and sulfur Isotope dependence of the Fe-S vibrational inodes can be used to distinguish mononuclear, blnuclear, and tetranuclear clusters. Hydrogen bonding of both Fe-0 and Fe-S clusters can be detected by frequency shifts in deuterium-substituted proteins. 

Isotope effects have also been investigated for the case of hydrogen-deuterium substitution in (C6H5)2PH, C6H5PH2,(1967 30) HPO20, HP(0)(0CH3)2 and other examples. a967 42) Lastly, temperature and solvent effects have also been considered for a variety of cases. (1967>4310... 

That work has shown that deuterium substitution produced very large kinetic isotope effects on the initiation step (a) and much smaller but still sizable effects on propagation step (d) ... 

In a variety of ways, deuterium-substituted reactants can provide vital information on dynamics Substantial isotope effects point to vibrational modes playing a key role in dynamics, and vice versa. 

As a theoretical model, diastereotopically distinct isotopic substitution in 1,3-butadiene was utilized by Bach and coworkersl9b to provide an independent test of the ability of high-level ab initio calculations to accurately predict a transition structure for epoxidation. The calculated KIE for deuterium substitution at the a-carbon in the TS for epoxidation of 1,3-butadiene (Figure 24) (Ha) is 0.99, in excellent agreement with the experimental value for an aryl-substituted styrene. The KIE for diastereotopically distinct hydrogen (Ht,) on the /J-carbon cis to the vinyl substituent is 0.80, while that for Hc is predicted to be 0.82. The calculated KIE is 0.66 for this transition structure with Hc, reflecting the extensive... 

Any vibration for which the frequency decreases on going to the transition state contributes a factor greater than 1 to (cH/A D, and any vibration for which the frequency increases contributes a factor less than 1. A commonly observed secondary isotope effect occurs when deuterium substitution is made at a carbon that changes hybridization, as in Equations 2.77 and 2.78. 

Deuterium substitution on the four carbon atoms changing from trigonal to tetrahedral as the reaction proceeds, gives rise to inverse secondary kinetic isotope effects, small but measurable, both for the diene and the dienophile 3.1. If both bonds are forming at the same time, the isotope effect when both ends are deuterated is geometrically related to the isotope effects at each end. If the bonds are being formed one at a time, the isotope effects are arithmetically related. It is a close call, but the experimental results, both for cycloadditions and for cycloreversions, suggest that they are concerted. 

In general, deuterium substitution can be used to decide which hydrogen atom in a molecule is the one most concerned in transfer processes. Introduction of deuterium at this position will reduce the transfer constant, and if transfer is accompanied by retardation, it will also reduce the extent of retardation. For work of this type, tritiumlabelling of the additive is not suitable substances so labelled usually contain only a very small proportion of molecules actually containing tritium and although there is a large isotope effect with these molecules, their number is so small relative to that of the unlabelled molecules that their influence cannot be detected. 

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