Nitrogen kinetic isotope effect

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. 

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 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). 

Disproportionation (equation 13) is one of the side reactions that can occur in benzidine rearrangements. Shine and coworkers measured the nitrogen and carbon kinetic isotope effects for the disproportionation reaction of 4,4 -diiodohydrazobenzene, which only yielded disproportionation products, at 25 °C in 70% aqueous dioxane that was 0.376 M in perchloric acid29. The reaction was first order in hydrazobenzene and it has been assumed that an intermediate was involved in the disproportionation reaction. This intermediate must be one of a radical ion30 (equations 14 and 15), a jr-complex31 (equation 16) or a quinonoid structure32 (equation 17). 

TABLE 1. The nitrogen, carbon-13 and secondary hydrogen-deuterium kinetic isotope effects found for the one- and two-proton benzidine rearrangements... 

TABLE 2. The nitrogen and carbon-13 kinetic isotope effects for the acid-catalyzed and for the thermal benzidine rearrangement of 2,2 -hydrazonaphthalene in 70% aqueous dioxane at 0°C and in 95% ethanol at 80 °C, respectively... 

Nitrogen, carbon-13 and carbon-14 kinetic isotope effects have been determined38 for the analogous acid-catalyzed ortho,ortho -rearrangement of the Af-2-naphthyl-Ar/-phenylhydrazine (equation 24). The labelled compounds required for this study were prepared by the sequence of reactions shown in Schemes 20-22. 

The nitrogen kinetic isotope effect of 1.0197 found using the substrate with the natural abundance of nitrogen isotopes corresponds to an isotope effect of 1.04 for the reaction of the doubly labelled compound. Thus, the nitrogen isotope effects found using two different analytical techniques to measure the isotope effect are in excellent agreement. 

TABLE 3. The nitrogen, the carbon-13 and carbon-14 kinetic isotope effects found for the acid-catalyzed ortho,ortho1-rearrangement of iV-naphthyl-iV-phenyl-hydrazine in 60% aqueous dioxane at 0°C... 

Rhee and Shine39 used an impressive combination of nitrogen and carbon kinetic isotope effects to demonstrate that a quinonoidal-type intermediate is formed in the rate-determining step of the acid-catalyzed disproportionation reaction of 4,4 -dichlorohydrazobenzene (equation 26). When the reaction was carried out at 0°C in 60% aqueous dioxane that was 0.5 M in perchloric acid and 0.5 M in lithium perchlorate, extensive product analyses indicated that the major pathway was the disproportionation reaction. In fact, the disproportionation reaction accounted for approximately 72% of the product (compounds 6 and 7) while approximately 13% went to the ortho-semidine (8) and approximately 15% was consumed in the para-semidine (9) rearrangement. 

The reaction was second order in acid and first order in substrate, so both rearrangements and the disproportionation reaction proceed via the doubly-protonated hydrazobenzene intermediate formed in a rapid pre-equilibrium step. The nitrogen and carbon-13 kinetic isotope effects were measured to learn whether the slow step of each reaction was concerted or stepwise. The nitrogen and carbon-13 kinetic isotope effects were measured using whole-molecule isotope ratio mass spectrometry of the trifluoroacetyl derivatives of the amine products and by isotope ratio mass spectrometry on the nitrogen and carbon dioxide gases produced from the products. The carbon-12/carbon-14 isotope... 

The most recent addition to Shine s extensive study of the benzidine-type rearrangements41 involved remeasuring the nitrogen and the carbon-13 and carbon-14 kinetic isotope effects at the 4- and at the 4- and 4 -carbons as well as determining the carbon-13 and carbon-14 isotope effects at the 1- and at the 1- and l -carbons in the benzidine rearrangement of hydrazobenzene (equation 30). The reaction, which was carried out in 75% aqueous ethanol that was 0.1 M in hydrochloric acid and 0.3 M in lithium chloride at 0°C, gave an 86% yield of benzidine (11) and a 14% yield of diphenyline (12). The kinetic isotope effects found for the formation of benzidine and diphenyline under these reaction conditions are presented in Table 5. 

The significant nitrogen, carbon-13 and carbon-14 kinetic isotope effects at the 4- and at the 4 and 4 -positions for the formation of benzidine (11) indicate that benzidine is formed in a concerted reaction. The small, but real, carbon-13 and carbon-14 kinetic... 

The nitrogen and carbon-13 kinetic isotope effects found using the N- N, die 1,1/-13C2 and die 4,4/-13C2 substrates were measured by whole-molecule isotope ratio mass spectrometry on die bis-(triduoroacetyl) derivative. 

Matsson and coworkers have measured the carbon-1 l/carbon-14 kinetic isotope effects for several Menshutkin reactions (equation 35) in an attempt to model the S/v2 transition state for this important class of organic reaction. These isotope effects are unusual because they are based on the artificially-made radioactive carbon-11 isotope. The radioactive carbon-11 isotope is produced in a cyclotron or linear accelerator by bombarding nitrogen-14 atoms with between 18- and 30-MeV protons (equation 36). 

Other workers have concluded that the transition state for the Menshutkin reaction is late with more nitrogen-alpha carbon bond formation than alpha carbon-leaving group bond rupture. For instance, Harris and coworkers51 found that the secondary alpha deuterium kinetic isotope effects (Table 8) decreased when a poorer nucleophile was used in the S v 2 reactions between 3,5-disubstituted pyridines and methyl iodide in 2-nitropropane at 25 °C (equation 38, Table 8). 

TABLE 7. The incoming nucleophile nitrogen kinetic isotope effects in Menshutkin reactions with various amines in several solvents ... 

The nitrogen (leaving group) kinetic isotope effects indicate that there is no change in the amount of 0 —N bond rupture in the S 2 transition state when the substitutent in the... 

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