Isotope effects, secondary deuterium

Methylene-l-pyrazoline Secondary deuterium isotope effects on the reaction rate 81CJC2556... 

Important additional evidence for aryl cations as intermediates comes from primary nitrogen and secondary deuterium isotope effects, investigated by Loudon et al. (1973) and by Swain et al. (1975 b, 1975 c). The kinetic isotope effect kH/ki5 measured in the dediazoniation of C6H515N = N in 1% aqueous H2S04 at 25 °C is 1.038, close to the calculated value (1.040-1.045) expected for complete C-N bond cleavage in the transition state. It should be mentioned, however, that a partial or almost complete cleavage of the C — N bond, and therefore a nitrogen isotope effect, is also to be expected for an ANDN-like mechanism, but not for an AN + DN mechanism. 

For an elegant study of the secondary deuterium isotope effects on a non-Schenck sensitized cis-trans isomerization, see Refs. 85-87. 

Tetrahedral intermediates, derived from carboxylic acids, spectroscopic detection and the investigation of their properties, 21, 37 Topochemical phenomena in solid-state chemistry, 15, 63 Transition state structure, crystallographic approaches to, 29, 87 Transition state structure, in solution, effective charge and, 27, 1 Transition state structure, secondary deuterium isotope effects and, 31, 143 Transition states, structure in solution, cross-interaction constants and, 27, 57 Transition states, the stabilization of by cyclodextrins and other catalysts, 29, 1 Transition states, theory revisited, 28, 139... 

Transition stale structure, secondary deuterium isotope effects and, 31, 143 Transition states, structure in solution, cross-interaction constants and, 27, 57 Transition states, the stabilization of by cyclodextrins and other catalysts, 29, 1 Transition states, theory revisited, 28, 139... 

The secondary deuterium KIEs obtained by converting the secondary tritium KIEs found for the E2 reactions of several different 2-arylethyl substrates into secondary deuterium KIEs with the Swain-Schaad equation (Swain et al., 1958) are in Table 36. As discussed above, one would expect the secondary deuterium isotope effect to reflect the extent to which rehybridization of the /3-carbon from sp3 of the reactant to sp2 in the product has taken place in the transition state. According to this reasoning, the secondary tritium EIE should be a good estimate of the maximum secondary tritium KIE. Because these reactions were not reversible, the EIE could not be measured. However, one can estimate the EIE (the maximum expected secondary KIE) using Hartshorn and Shiner s (1972) fractionation factors. The predicted EIE (Kh/Kd) values were 1.117 at 40°C and 1.113 at 50°C. Seven of the reactions... 

In reaction (10.11) the deuterium isotope effect is a secondary isotope effect, that is one in which the bonding to the isotopically substituted atom is not broken or formed during the course of the reaction. Secondary deuterium isotope effects are generally much smaller than primary ones. 

Fig. 10.12 (a) Transition state structures (C—C bond lengths) calculated at two levels for the concerted and step-wise Diels-Alder reaction shown in Fig. 10.11 (Houk, K. N., Gonzalez, J., and Li, Y,Accts. Chem. Res. 28, 81 (1995). The parenthesized values show results for calculations at a much higher (and much more expensive) level, (b) Calculated secondary deuterium isotope effects, kH/kD (per D) for the concerted and stepwise Diels-Alder reactions shown in Fig. 10.11 (Houk, K. N., Gonzalez, J., and Li, Y,Accts. Chem. Res. 28, 81 (1995). The parenthesized values show results for calculations at a much higher (and much more expensive) level)...

A label (L = D or T) can be introduced in the transferable position (left subscript of the rate constant) or in the non-transferable position (right subscript of the rate-constant) Then A hh/ dh hd/ dd primary deuterium isotope effects, while hh/ hd dh/ dd secondary deuterium isotope effects. In the general case, we can relate each of the two effects by ... 

Cook, P.F., Blanchard, J.S. and Cleland, W.W. (1980). Primary and secondary deuterium isotope effects on equilibrium constants for enzyme-catalyzed reactions. Biochemistry 19, 4853-4858... 

Ab initio MO calculations have been carried out for two carbocation-generating reactions the 6 nI reaction of protonated 1-phenylethanol (H2O leaving group) and the acid-catalysed hydration of styrene. Optimizations were done at the MP2/6-31G level. The 6 nI transition state lies half way between the reactant and the product with respect to the bond lengths, charge distribution, and secondary deuterium isotope effects. 

Shift reagents have been employed to study the kinetics of catalytic deuteria-tion of 4-t-butylcyclohexanone, and secondary (deuterium) isotopic effects in organic substrates. The n.m.r. study of internal rotation of the methyl groups in MOjNCOR (R = H, Me, or Et) has been facilitated using (1 Ln = Eu or Pr, R = C3F7, R2 = BuV ... 

However, quantitative evaluation of the size of this preference depended on knowing the size of the secondary deuterium isotope effect on which C—C bond in 7b cleaves. With the seemingly reasonable assumption of a secondary isotope effect of 1.10 on bond cleavage, the experimental data led to the conclusion that double methylene rotation was favored over single methylene rotation by a factor of 50 in the stereomutation of 7b. Although the error limits on the measurements were large enough to allow the actual ratio to be much smaller, Berson wrote, There is no doubt that the double rotation mechanism predominates by a considerable factor. ... 

Sixteen years later Baldwin and co-workers published the results of even more elegant experiments in which the stereomutation of optically active 7-l- C-l,2,3-was studied. Because a deuterium atom is attached to each of the carbons in this compound, it was unnecessary for Baldwin to assume the size of a secondary deuterium isotope effect on which bond cleaves, in interpreting his kinetic data. The results of his experiments led him to conclude, the double rotation mechanism does not predominate by a substantial factor. ... 

These recent calculations for cyclopropanes and trimethylene transition structures, and for isotopically labeled analogs, have provided vibrational frequencies from which secondary deuterium isotope effects have been calculated. Getty, Davidson and Borden found that reactions dependent upon C,(ts) at 422.5 °C should be associated with secondary deuterium kinetic isotope effects favoring access to 1,2-d2-Cj(ts) over l,3-d2-C (ts) structures by a factor of 1.13269. 

Crawford and Tagaki have examined gas-phase decompositions of several azo compounds with R = CH3, /-butyl, or allyl they found that most of these compounds, both symmetric and unsymmetric, decompose by the noncon-certed path (Equation 9.29).87 Seltzer found by studying secondary deuterium isotope effects that in unsymmetrical azo compounds in which one R group is a much better radical than the other, the bond breaking is stepwise.68 In a compound such as 20, substitution of the hydrogen on the a-phenylethyl side gives... 

Long-lived cyclopropylcarbinyl cation chemistry, including spiro cations and dications, has been reviewed,7 and some of the more interesting newer carbocations, such as (1), are the subject of a short survey.8 The use of secondary deuterium isotope effects in the study of carbocation-forming reactions has been revisited,9 and the... 

Secondary deuterium isotope effects are important in the study of neighbouring-group participation in solvolytic reactions.61 This subject has now been reviewed at considerable length. Other evidence bearing on participation is also discussed. 

Retro-cycloaddition extrusion of the metaphosphate moiety from 2,3-oxa-phosphabicyclo[2.2.2]octene derivatives (79), in 1,2-dichloroethane at 100 °C in the presence of PrOH, has been shown to proceed via an unsymmetrical transition state in which C—P bond breakage and P=0 bond formation are more advanced than C—O breakage.39 The secondary deuterium isotope effect on H adjacent to the P—C bond is 1.060 0.008 for (79a) and 1.081 0.009 for (79b) and the oxygen kinetic isotope effect on the P—O—C bridge is 0.9901 0.0016 for (79a). 

To ascertain the origin of the large -effect in the antiperiplanar geometry, a-secondary deuterium isotope effects were measured for the solvolysis of 1543. 

The cis isomer 52 was found to react about 450 times faster than its unsilylated analogue 51 in 97% trifluoroethanol. However, the turns isomer 53 showed essentially no acceleration. The secondary deuterium isotope effect observed with the fi tetradeuterated analogue of the cis isomer 52 confirmed that the molecule reacts via the diequatorial conformation. In this conformation the back lobes of the Si—C bond at the 3-position can interact with the developing p orbital at the 1-position. This through-space interaction is often referred to as homohyperconjugation. 

The inductive effect of the donating C—D bonds to the observed large inverse secondary deuterium isotope effect has not been given proper consideration but treated as a rather minor component superimposed on the important steric component caused by larger amplitudes of vibrations of C—H bonds than those of the C—D bonds. 14C KIE have not been studied in this reaction. The C2, C V. C3 , C3, endo hydrogens are separated only by 2.11 A, substantially less than van der Waals radii (2 x 1.2 A)404. 

---