Deuterium inverse

The large inverse deuterium isotope effects, that is the ratio of the formation rates for CsDfiO and C3HgO, nj/rir of 3-5, much greater than the possible range of the true deuterium inverse isotope effects3, have been rationalized qualitatively within the framework of the reaction scheme (equation 1), by assuming that C—H versus C—D bond rupture determines the further total oxidation of the intermediate, common to both epoxide formation and full oxidation to C02. 

Graham showed that the rate of diffusion of different gases through a porous diaphragm was inversely proportional to the square roots of their densities this is the basis of a method of separation of gases, and has been applied successfully to the separation of hydrogen and deuterium. 

TABLE 2-157 Approximate Inversion-Curve Locus for Deuterium... 

Nucleophilic substitution in cyclohexyl systems is quite slow and is often accompanied by extensive elimination. The stereochemistry of substitution has been determined with the use of a deuterium-labeled substrate (entry 6). In the example shown, the substitution process occurs with complete inversion of configuration. By NMR amdysis, it can be determined that there is about 15% of rearrangement by hydride shift accon any-ing solvolysis in acetic acid. This increases to 35% in formic acid and 75% in trifiuoroacetic acid. The extent of rearrangement increases with decreasing solvent... 

When the exchange is carried out on a (25S)-spirostan derivative (50) the compound undergoes epimerization at C-25. During this inversion about 20 % deuterium is incorporated" at C-25 [(51), R = D]. This observation is consistent with the various mechanisms which have been proposed for this... 

This is most readily studied with cyclohexane- /n in which 11 of the 12 protons are replaced with deuterium. The spectrum of cyclohexane- /n resembles the behavior shown in Fig. 4-8 at about — 100°C (the slow exchange regime) two sharp lines are seen these broaden as the temperature is increased, reaching coalescence at — 61.4°C, and becoming a single sharp line at higher temperatures. (The deuterium nuclei must be decoupled by rf irradiation.) Rate constants t for the conversion were measured over the temperature range — 116.7°C to — 24.0°C by Anet and Bourne. It is probable that the chair-chair inversion takes place via a boat intermediate. 

Since the conformational inversion of 2c-methylcyclohexanone is the key step in this sequence, the corresponding conformationally more stable system, i.e., cw-2-methyl-4-t-butylcyclohexanone (14), should fail to incorporate any deuterium. This was actually shown to be the case. Treatment of this ketone under identical conditions for d exchange did not show any d incorporation. This evidence also rules out the likelihood of any d incorporation via acid- or base-catalyzed enolization. 

The amino acid methionine is formed by a melhylation reaction of homo cysteine with iV-methyltetrahydrofolate. The stereochemistry of the reactior has been probed by carrying out the transformation using a donor with a "chiral methyl group" that contains protium (H), deuterium (D), and tritium (T isotopes of hydrogen. Does the methylation reaction occur with inversion oi retention of configuration ... 

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... 

Apart from a few studies (ref. 7), the use of deuterium kinetic isotope effects (kie s) appears to have had limited use in mechanistic studies of electrophilic bromination of olefins. Secondary alpha D-kie s have been reported for two cases, trans-stilbene fi and p-substituted a-d-styrenes 2, these giving relatively small inverse kie s of... 

What we have shown here is the fact that large inverse values can be obtained for the Br2 addition to a "normal" olefin which should pass through a symmetrical, or nearly so, transition state. Of course, more work involving other systems would be beneficial in assessing the scope and limitation of the use of the a-deuterium kie s in mechanistic studies of Br2 and Br3 reactions with olefins. 

Data from microwave spectra on the centrifugal effect of rotational transitions of selenophene and its deuterium-substituted derivatives have been determined experimentally and compared with the calculated theoretical values of the centrifugal stretching constants by means of the force constants determined from the solution of the inverse vibrational problem.26 The two sets of values show good agreement, indicating that the system of force constants obtained for selenophene correctly reflects the characteristic features of the force field of the molecule. 

F. Kinetic Isotope Effect. One of the more important observations regarding the cobalt-based homogeneous CO hydrogenation system is that the substitution of gaseous deuterium for gaseous hydrogen causes an inverse (i.e. kflkinetic isotope effect, kj T2)/kH(2)= 0.73 at 180° in p-dioxane (13b). Because... 

The observed normal isotope effect of 1.9 provides further evidence supporting the role of Asp55 as the general base. Namely, a normal isotope effect of 1.9 is most consistent with general base catalysis by an amino acid side chain, as inverse isotope effects are commonly observed when a zinc-bound water molecule, or hydroxide, is the attacking nucleophile. For example, the zinc-containing enzymes AMP deaminase [111], thermolysin [112], stromelysin [113], and a desuccinylase [114] are each believed to utilize a zinc-bound water as the nucleophile, and all of these reactions are characterized by an inverse deuterium isotope effect. This inverse isotope effect is thought to result from a dominant... 

---