Hydrogen bonding and deuterium isotope effects

Isotope Effect and Hydrogen Bond Type. Singh and Wood (146) have calculated using Stepanov s approximation the effect of isotopic substitution of hydrogen by deuterium on the R(A..B) distance of an A—H.. B hydrogen bond. They found that the R(A.. B) distance increases (positive isotope effect) on deuteration if the potential energy... 

As we have discussed in depth elsewhere, despite the similarities in the structures of hypericin and hypocrellin, which are centered about the perylene quinone nucleus, their excited-state photophysics exhibit rich and varied behavior. The H-atom transfer is characterized by a wide range of time constants, which in certain cases exhibit deuterium isotope effects and solvent dependence. Of particular interest is that the shortest time constant we have observed for the H-atom transfer is 10 ps. This is exceptionally long for such a process, 100 fs being expected when the solute H atom does not hydrogen bond to the solvent [62]. That the transfer time is so long in the perylene quinones has been attributed to the identification of the reaction coordinate with skeletal motions of the molecule [48, 50]. 

Section 5.17 A P C—D bond is broken more slowly in the E2 dehydrohalogenation of alkyl halides than a p C—H bond. The ratio of the rate constants / h/ d is a measure of the deuterium isotope effect and has a value in the range 3-8 when a carbon-hydrogen bond breaks in the rate-determining step of a reaction. 

The transformation of the intermediate, I, to the final product, N-allyl-2,4-dinitroanilme, involves the breaking of both a carbon-chlorine bond and a nitrogen-hydrogen bond. Whether this takes place in two consecutive steps or in a single, concerted process, a valid mechanism must be consistent with both the absence of a measurable deuterium isotope effect and the fact that the observed rates are affected by the process in which the nitrogen-hydrogen bond is broken. 

A second 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-hydrogen bond is weaker by about 5 kj/mol (1.2 kcal/mol) than the corresponding carbon-rfaiiferiwm 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. For instance, the base-induced elimination of HBv from l-bromo-2-phenylethane proceeds 7.11 times as fast as the corresponding... 

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 ... 

A primary isotope effect results when the breaking of a carbon-hydrogen versus a carbon-deuterium bond is the rate-limiting step in the reaction. It is expressed simply as the ratio of rate constants, i wlky,. The full expression of k /kn measures the intrinsic primary deuterium isotope for the reaction under consideration, and its magnitude is a measure of the symmetry of the transition state, e.g., -C- H- 0-Fe+3 the more symmetrical the transition state, the larger the primary isotope effect. The theoretical maximum for a primary deuterium isotope effect at 37°C is 9. The less symmetrical the transition state, the more product-like or the more substrate-like the smaller the intrinsic isotope effect will be. 

To explore the mechanism of allylic hydroxylation, three probe substrates, 3,3,6,6-tetradeuterocyclohexene, methylene cyclohexane, and /l-pinenc, were studied (113). Each substrate yielded a mixture of two allylic alcohols formed as a consequence of either retention or rearrangement of the double bond. The observation of a significant deuterium isotope effect (4-5) in the oxidation of 3,3,6,6-tetradeuterocyclohexene together with the formation of a mixture of un-rearranged and rearranged allylic alcohols from all three substrates is most consistent with a hydrogen abstraction-oxygen rebound mechanism (Fig. 4.48). 

In reactions 14.32 and 14.33 the hydrogen atoms are not involved in any bonds that are being made or being broken in the reaction. The isotope effect is therefore referred to as a secondary a-deuterium isotope effect since the position of isotopic substitution is a to the bond being broken in the rate limiting step (see Chapter 10 for discussion of secondary isotope effects). 

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