The Deuterium Isotope Effect

One final piece of evidence in support of the E2 mechanism is provided by a phenomenon known as the deuterium isotope effect. For reasons that we won t go into, a carbon-liydrcgen bond is weaker by a small amount [about 5 kJ/mol (1.2 kcal/mol)l than a corresponding esrhon-deuterium bond Thus, a C-H bond is more easily broken than an equivalent C-D bond, and the rate of C-H bond cleavage is faster. As an example of how this effect can be used to obtain mechanistic information, the base-induced elimination of HBr from l-bromo-2-phenylethane proceeds 7.11 times as fast as the corresponding elimination of DBr from l-bromo-2,2-dideuterio-2-phenylethane  

This result tells us that the C-H (or C-D) bond is broken in the rate-limiting step, consistent with our picture of the E2 reaction as a one-step process. If it were otherwise, we couldn t measure a rate difference. 

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Figure 1.9. NMR spectra of a mixture of ethanol and hexadeuterioethanol [27 75 v/v, 25 °C, 20 MHz], (a) H broadband decoupled (b) without decoupling. The deuterium isotope effect Sch - d on chemical shifts is 1.1 and 0.85 ppm for methyl and methylene carbon nuclei, respectively...

The deuterium isotope effect is thought to arise from the effect on the equilibrium position of this A-nitrosation. This is also the case for the diazotization of aniline, but the isotope effect is larger, because two deprotonations are involved in the kinetics. 

The deuterium isotope effect for each hydrogen atom ortho to the diazonio group ( H/ D = 1.22, Swain et al., 1973b) is the largest secondary aromatic hydrogen isotope effect yet observed. It is comparable to those observed for a-deuterium in reactions involving carbocation formation from secondary aliphatic esters. Ob-... 

If the deuterium isotope effect on the rearrangement rate ( H/ D3)r is larger than unity and is approximately equal to that on the rate of dediazoniation ( H/ D3)S, it can be concluded that the ion-molecule pair 8.13 is the more likely intermediate for the rearrangement reaction. On the other hand, an isotope effect on the rearrangement rate that is smaller than or equal to unity would indicate the involvement of the benzenespirodiazirine cation 8.17 as an intermediate. 

Investigation of water motion in AOT reverse micelles determining the solvent correlation function, C i), was first reported by Sarkar et al. [29]. They obtained time-resolved fluorescence measurements of C480 in an AOT reverse micellar solution with time resolution of > 50 ps and observed solvent relaxation rates with time constants ranging from 1.7 to 12 ns. They also attributed these dynamical changes to relaxation processes of water molecules in various environments of the water pool. In a similar study investigating the deuterium isotope effect on solvent motion in AOT reverse micelles. Das et al. [37] reported that the solvation dynamics of D2O is 1.5 times slower than H2O motion. 

FIGURE 2.11. 19F NMR spectrum of l,6-difhiorohexane-l,l-d2, demonstrating the deuterium isotope effect on the fluorine chemical shift... 

Taking into consideration the deuterium isotope effect (k Yfy/kxfD) = 2.3), they concluded that fca< k a< /cb and that the rate-determining step was the first substitution. Ligand substitution was thought to proceed by the Ia mechanism, on the basis of the negative AS and the independence of the rate on the concentration of acetylacetone. This feature is compatible with the results with tris(acetylacetonato)metal(III) previously obtained [21]. Furthermore, in the second transition series the kt value decreases in the order... 

The measurement of deuterium isotope effects on chemical shifts is a useful tool for studies of tautomeric equilibrium (for details see the reviews 42 44). The deuterium isotope effect AX(D) is defined as the difference between chemical shifts in deuterated and non-deuterated sample [26]. 

The deuterium isotope effects on chemical shift consists of intrinsic isotope effect (direct perturbation of the shielding of X atom) and equilibrium isotope effect (perturbation of the equilibrium caused by the isotopic substitution). The values of deuterium isotope effects are to some extent independent of chemical shifts and allow determination of the mole fraction of the forms in equilibrium. 

Hansen et al.52 measured the deuterium isotope effects for the Schiff base being a derivative of racemic gossypol [7]. The high negative value of deuterium isotope effect observed at carbon C-7 linked with proton donor group (—190 — 240 ppb), solvent and temperature independent, clearly indicated the existence of this compound as enamine-enamine tautomer. 

Measurements of the deuterium isotope effect for unsymmetrical di-Schiff bases fully confirmed the interrelation between proton transfer equilibria in both intramolecular hydrogen bonds.46... 

The effect of deuterium isotope substitution on Tc has been studied for three members of the KL-(BEDT-TTF)2Ag(CF3)4(l,l,2-trihaloethane) family [12, 34-36]. In all cases, the Tc increased upon deuteration with the effect ranging from 0.21 to 0.36 K. These results are similar to the deuterium isotope effect observed in the p"-(BEDT-TTF)2SF5CH2CF2S03 [34, 37] and k-(BEDT-TTF)2Cu(NCS)2 [38] superconductors. 

They both produce the same intermediate, and because of the deuterium isotope effect, more hydrogen is lost than deuterium. 

Prakash et al. (1985) used the deuterium isotope effect on the l3C NMR spectrum of [47] to provide further evidence for the symmetrical, homoaromatic nature of this ion. They prepared the specifically deuterated trishomocyclopropenyl cation [57] by superacid treatment of the corresponding alcohol [58]. The 13C NMR spectrum of [57] displayed a triplet for the deuterated methine only 0.2 ppm to higher field than the undeuterated methine, indicating only an isotopic perturbation of resonance and not a rapidly equilibrating classical ion system (see Siehl, 1987). 

There have been numerous kinetic studies of the deuterium isotope effect for proton and hydrogen atom transfer where values for EH — Ev greatly exceed 1.4kcal/mol and the ratio of A factors, AD/AH, are significantly >1.4 values >10 are very common [4]. These observations directly challenge the classical model for proton transfer based upon transition state theory that neglects contributions from k. 

The 13 C resonances in derivatives of aniline reveal that the carbon bearing a partially deuterated NH2 group appears as a multiplet because of the deuterium isotope effect on the 13C chemical shift, when the hydrogen exchange is low. This effect is larger for... 

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. 

The ratio of products (36) and (37) from VNS of hydrogen (Pe) and substimtion of halogen (Px), respectively (Scheme 4), will depend on the strength and concentration of base, provided that the elimination is a kinetically important step in the VNS reaction, namely Pr/Px = kikE[B]/k-ikx. The influence of base will decrease until a constant value Ph/Px = k /kx is reached as kslB] k i. This has been demonstrated for 4-chloronitrobenzene, which undergoes exclusive substimtion of chlorine unless strong base is present to favour the VNS process. The deuterium isotope effect for VNS hydroxylation by Bu OOH, determined as me ratio of H versus D substitution of l-deutero-2,4-dinitrobenzene, varied from 7.0 0.3 to 0.98 0.01 as the base in NH3 was changed from NaOH to Bu OK me former value is consistent with a rate determining E2 process. 

The deuterium isotope effect on homogeneous electron-transfer reactions has been noted for cation-radicals, too. Gronheid et al. (2003) observed the effect for cation-radicals of biphenyl and... 

This mechanism seems to imply that if some substitution occurs at the classical position of attack (the first a-complex), then such a substitution should show the deuterium isotope effect for proton loss from this position. The deuterium effect is absent in the majority of nitration cases, except for nitration in sterically shielded positions (Schoffield 1980). Perhaps a systematic investigation of... 

Fig. 5A The dependence on pH of the deuterium isotope effect in the hammerhead ri-bozyme-catalyzed reaction. Black circles show rate constants in H2O gray circles show rate constants in D2O. Solid curves are experimentally determined curves. The apparent plateau of cleavage rates above pH 8 is due to disruptive effects on the deprotonation of uridine and guanosine residues. Dotted lines are theoretical lines calculated from pKa values of hydrated Mg ions of 11.4 in H2O and 12.0 in D2O and on the assmnption that there is no intrinsic isotope effect (a=kH2o/kD2o=l is the coefficient of the intrinsic isotope effect). The following equation was used to plot the graph of pL vs log(rate) log kobs=log(kmax)-log(l+10

Reaction of atomic carbon with alkenes generally involves both DBA and vinyl C—H insertion. An interesting example is the reaction of C atoms with styrene in which the major products are phenylallene (21) and indene (22). The synthesis of a number of specifically deuterated styrenes and the measurement of the deuterium isotope effects on the 21/22 ratio led to the conclusion that 21 was formed by DBA followed by ring expansion and by C—H(D) insertion into and followed by rearrangement of the resultant frawi-vinylcarbene (23). The indene was formed by C—H(D) insertion into Xb followed by cyclization of the resultant cw-vinylcarbene (24) (Eq. 18). An examination of the product ratios and their label distributions when atoms are used leads to the conclusion that the ratio of C=C addition to C—H insertion is 0.72 1 in this case. 

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