Nitrogen isotope effects

A small preference for the involvement of the N-1 nitrogen is observed in the loss of HCN from the molecule of N-labelled indazole (80OMS533). In addition, there is a small isotope effect (1.08). 

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. 

A true intramolecular proton transfer in the second step of an azo coupling reaction was found by Snyckers and Zollinger (1970a, 1970b) in the reaction of the 8-(2 -pyridyl)-2-naphthoxide ion (with the transition state 12.151). This compound shows neither a kinetic deuterium isotope effect nor general base catalysis, in contrast to the sterically similar 8-phenyl-2-naphthoxide ion. Obviously the heterocyclic nitrogen atom is the proton acceptor. 

White et al.1A have obtained similar kinetic results for the acid-catalysed rearrangement of N-nitro-N-methylaniline, i.e. a first-order dependence on the nitroamine with a linear H0 plot of slope 1.19 for phosphoric acid, and a deuterium solvent isotope effect of about three, although the results have only been presented in preliminary form. Further, an excellent Hammett a+ correlation was claimed for thirteen para substituted nitroamines which gave a p value of —3.9. Since it is expected that the rate coefficients would correlate with a (rather than different basicities of the amines, the a+ correlation implies that the amino nitrogen is electron-deficient in the transition state,... 

One way to determine just where a given reaction stands on the El-E2-ElcB spectrum is to study isotope effects, which ought to tell something about the behavior of bonds in the transition state. For example, CH3CH2NMe3 showed a nitrogen isotope effect of 1.017, while PhCH2CH2NMe3" gave a corres-... 

Ambrose focuses on stable nitrogen isotope ratios and reports the results of controlled diet and climate experiments on rats. He explores trophic level differences and heat stress and their effects on stable isotopes of nitrogen. As with the preceding chapters by Schwarcz and Hedges and van Klinken, Ambrose explores the various biochemical principles that explain why variation is expected under these circumstances. 

The kinetic isotope effect of the protonation h/ d = 3.9 suggests that an in-nitrogen atom is protonated directly rather than conformational changes exposing the lone pair of a nitrogen atom to the outside prior to protonation. It is assumed that a protonated nitrogen does not invert. Inversion is only possible by a deprotonation-inversion-reprotonation sequence (Kjaer etal., 1979). 

The nitrogen kinetic isotope effect for this reaction is 1.034 0.002, which indicates that breaking of the N-O bond occurs in the slow step. ... 

The Fe(II) reduction of nitrate displays a nitrogen isotope effect of... 

This is the same mechanism as that given above for esters, in equation (42). The difference between esters and amides is apparent from a comparison of the two tetrahedral intermediates [5] and [17], The former contains three oxygens, any of which can be protonated, resulting in much lsO exchange being observed when the reaction takes place in 180-enriched water,275,276 but [17] contains a much more basic nitrogen, which will be protonated preferentially and lead to much less 180 exchange, as observed.274 277,278 Also, ammonium ion formation makes the overall reaction irreversible, unlike ester hydrolysis. The calculated solvent isotope effect for the Scheme 15 process is 1.00,280 exactly in accord with experimental observation.278,279... 

The k pathway is three times faster in D+/D20 than in H+/H20 for la. The reverse kinetic isotope effect suggests that the rate-limiting event for the k pathway could involve protonation of an amido-nitrogen or an N-Fe bond, forming the stronger N-H bond as the weaker N-Fe bond is cleaved. The k 3 pathway is rationalized as involving pre-equilibrium peripheral protonations of the TAML macrocycle (Scheme 1). The dependence of obs on [H + ] is then given by Eq. (4), which corresponds... 

In the mechanism study of /V-benzyl-/V -alkyl hydroxylamines, regarding oxidation with HgO and p-benzoquinone, it has been proposed on the basis of intra- and intermolecular kinetic isotope effects that, initially, there takes place a one-electron transfer from a nitrogen atom to the oxidant, with a subsequent proton abstraction (106—108). 

The important observation is that all of the isotope effects are large and inverse. Therefore, the transition states in these reactions must be very crowded, i.e. the Ca—H(D) out-of-plane bending vibrations in the transition state must be high energy (Poirier et al., 1994). As a result, these workers concluded that nitrogen-a-carbon bond formation is more advanced than a-carbon-iodine bond rupture in the transition state. It is interesting, however, that in spite of the small secondary a-deuterium KIEs, these authors concluded that the N—C bond formation is only approximately 30% complete in the transition state. 

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