Kinetic isotope effects nitration

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. 

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 ... 

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 ... 

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. 

Problem 11.6 Sulfonation resembles nitration and halogenation in being an electrophilic substitution, but differs in being reversible and in having a moderate primary kinetic isotope effect. Illustrate with diagrams of enthalpy H) versus reaction coordinate. ... 

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 kinetic isotopic effects would be useful in a much wider range of substrates in comparison with their ionization potentials and nitration conditions. 

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