Nitration isotope effects

Other inverse isotope effects have been found in some nitration reactions by Olah and co-workers (1961a) for benzene-dg, fiuorobenzene-4-d and toluene-dg (no. 6 and 9) and by Oestman (1962) for thiophene-2-t (no. 8). The measured effects are small and probably due to secondary a-effects. It might be added, that the accuracy of some other nitration isotope effects is insufficient to detect small inverse or normal secondary effects. It is not intended to include a discussion of secondary isotope effects in view of a forthcoming review by Halevi (1963). 

Melander first sought for a kinetic isotope effect in aromatic nitration he nitrated tritiobenzene, and several other compounds, in mixed acid and found the tritium to be replaced at the same rate as protium (table 6.1). Whilst the result shows only that the hydrogen is not appreciably loosened in the transition state of the rate-determining step, it is most easily understood in terms of the S 2 mechanism with... 

One way in which the step of the reaction in which the proton is lost might be slowed down, and perhaps made kinetically important (with i), would be to carry out nitration at high acidities. Nitration of pentadeuteronitrobenzene in 97-4% sulphuric acid failed to reveal such an effect. In fact, nitrations under a variety of conditions fail to show a kinetic isotope effect. 

Another circumstance which could change the most commonly observed characteristics of the two-stage process of substitution has already been mentioned it is that in which the step in which the proton is lost is retarded because of a low concentration of base. Such an effect has not been observed in aromatic nitration ( 6.2.2), but it is interesting to note that it occurs in A -nitration. The A -nitration of A -methyl-2,4,6-trinitroaniline does not show a deuterium isotope effect in dilute sulphuric acid but does so in more concentrated solutions (> 60 % sulphuric acid kjj/kjj = 4 8). ... 

A substantial body of data, including reaction kinetics, isotope effects, and structure-reactivity relationships, has permitted a thorough understanding of the steps in aromatic nitration. As anticipated from the general mechanism for electrophilic substitution, there are three distinct steps ... 

With very few exceptions, the final step in the nitration mechanism, the deprotonation of the ff-complex, is fast and therefore has no effect on the observed kinetics. The fast deprotonation can be confirmed by the absence of an isotope effect when deuterium or... 

Hartshorn and Ridd48 showed that there is a negligible solvent isotope effect on nitrating anilinium ions in sulphuric acid and deuterated sulphuric acid (cf. an earlier less accurate determination by Brickman and Ridd48). The absence of a solvent isotope effect also argues against reaction on the free base because the free base concentration would be lower by a factor of about four in the deuterium-containing medium. Consequently, the differences in the rate coefficients in Table 6... 

The log rate versus acid strength curve for the latter compound is of the exact form expected for reactions of the free base, whilst that of the former compound is intermediate between this form and that obtained for the nitration of aniline and phenyltrimethylammonium ion, i.e. compounds which react as positive species. That these compounds react mainly or entirely via the free base is also indicated by the comparison of the rate coefficients in Table 8 with those in Table 5, from which it can be seen that the nitro substituent here only deactivates weakly, whilst the chloro substitutent appears to activate. In addition, both compounds show a solvent isotope effect (Table 9), the rate coefficients being lower for the deuterium-containing media, as expected since the free base concentration will be lower in these. 

A small isotope effect has been observed in nitration of benzene by nitronium borofluoride in tetramethylene sulphone at 30 °C (kH/kD = 0.86) and this has been attributed to a secondary effect of the change in hybridisation from sp2 to sp3 of the ring carbon during the course of the reaction109. However, naphthalene gives an isotope effect of 1.15 under the same conditions, and anthracene a value of 2.6115. It does not seem at all clear why these relatively unhindered and normally more reactive molecules should give rise to an isotope effect when benzene does not. 

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

Kinetic isotope effects have not been observed for chlorination, and only rarely for bromination, i.e. the reactions normally follow pathway [2a] like nitration. In iodination, which only takes place with iodine itself on activated species, kinetic isotope effects are the rule. This presumably arises because the reaction is readily reversible (unlike other halogenations), loss of I occurring more often from the a complex (14) than loss of H, i.e. k, > k2 ... 

The formation of the Wheland intermediate from the ion-radical pair as the critical reactive intermediate is common in both nitration and nitrosation processes. However, the contrasting reactivity trend in various nitrosation reactions with NO + (as well as the observation of substantial kinetic deuterium isotope effects) is ascribed to a rate-limiting deprotonation of the reversibly formed Wheland intermediate. In the case of aromatic nitration with NO, deprotonation is fast and occurs with no kinetic (deuterium) isotope effect. However, the nitrosoarenes (unlike their nitro counterparts) are excellent electron donors as judged by their low oxidation potentials as compared to parent arene.246 As a result, nitrosoarenes are also much better Bronsted bases249 than the corresponding nitro derivatives, and this marked distinction readily accounts for the large differentiation in the deprotonation rates of their respective conjugate acids (i.e., Wheland intermediates). 

TABLE 12. The nitrogen (leaving group) and secondary alpha hydrogen-deuterium kinetic isotope effects for the S 2 reactions between several para-substituted sodium thiophenoxide and benzyldimethylphenylammonium nitrate in DMF at 0°C... 

TABLE 13. The secondary alpha hydrogen-deuterium and primary nitrogen kinetic isotope effects for the SN2 reaction between sodium thiophenoxide and benzyldimethylphenylammonium nitrate at different ionic strengths in DMF at 0 C... 

The nucleophile in the S.v2 reactions between benzyldimethylphenylammonium nitrate and sodium para-substituted thiophenoxides in methanol at 20 °C (equation 42) can exist as a free thiophenoxide ion or as a solvent-separated ion-pair complex (equation 43)62,63. The secondary alpha deuterium and primary leaving group nitrogen kinetic isotope effects for these Sjv2 reactions were determined to learn how a substituent on the nucleophile affects the structure of the S.v2 transition state for the free ion and ion-pair reactions64. 

TABLE 14. The secondary alpha deuterium kinetic isotope effects and primary leaving group nitrogen kinetic isotope effects for the free ion and ion-pair S 2 reactions between benzyldimethylphenylammonium nitrate and para-substituted thiophenoxide ions in methanol at 20 °C... 

Microbial reduction of nitrate to N2, known as denitrification, is similar. It is kinetically inhibited in the absence of bacteria and is known to induce a kinetic isotope effect (Blackmer and Bremner 1977 Kohl and Shearer 1978 Mariotti et al. 1981 Bryan et al. 1983 Htibner 1986 Mariotti et al. 1988). W N shifts ranging from 6.5%o to 20%o have been observed experimentally. As with sulfate, microbial fractionations appear to depend on the metabolic states of the microbes. 

Bruchert V, Knoblauch C, Jorgensen BB (2001) Controls on stable sulfur isotope fractionation during bacterial sulfate reduction in Arctic sediments. Geochim Cosmochim Acta 65 763-776 Bryan BA, Shearer G, Skeeters JL, Kohl DH (1983) Variable expression of the nitrogen isotope effect associated with denitrification of nitrate. J Biol Chem 258 8613-8617 Canfield DE (2001) Biogeochemistry of sulfur isotopes. Rev Mineral Geochem 43 607-636 Chau YK, Riley JP (1965) The determination of selenium in sea water, silicates, and marine organisms. Anal Chim Acta 33 36-49... 

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