Nitrenium ions structure

Density functional-based theoretical methods have been demonstrated to give highly accurate predictions of nitrenium ions structures, singlet-triplet energy gaps, and vibrational spectra. Future challenges in the area of theoretical predictions include the accurate modeling of nitrenium ion reactions and reaction rates. 

The ambivalent nature of an a-cyano group on a carbocationic center has been demonstrated by the solvolytic work of Gassman and co-workers.713 714 Inductively, the cyano group strongly destabilizing. However, the major portion of this effect is offset by the mesomeric nitrenium ion structure 283b. 

A paper has reported that nitrogen-centred radicals (29) have been generated by one-electron reduction (at carbon or metal electrodes) of stable nitrenium ions of the general structure (28). The reactivity of the radicals is influenced by the substituents attached to the two nitrogen atoms that are directly linked to the ion nitrenium centre." ... 

The nitrenium ion +NH2 has been the subject of a detailed, comprehensive calculation. Calculations on (48) with 15 different X substituents reveal a large substituent sensitivity, and also that aqueous solvation preferentially stabilizes the singlet state. This substiment sensitivity agrees with the results of a time-resolved IR study of the diphenylnitrenium ion (49), which shows that resonance contributors such as (50) and (51) are very important to the overall structure. Substituted 4-biphenyl nitrenium ions... 

As a class, nitrenium ions are rather poorly characterized relative to similar reactive intermediates such as carbenes and carbenium ions. This simation alone is sufficient to motivate many fundamental studies into their structures and behavior. There are also several practical considerations that motivate their study. The following is intended as a brief overview of these latter areas. 

It is now apparent that nitrenium ions occur in a variety of contexts including the so-called Bamberger rearrangement (i.e., acid-catalyzed isomerization of N-hydroxyaniline 14 to 4-aminophenol 15, Fig. 13.9), and the aforementioned catabolism of arylamines. The earlier workers, however, for the most part did not explicitly consider the possibility of such a species. Heller et al. were the first to present kinetic evidence for such an intermediate. Interestingly, they chose to represent it as the iminocyclohexadienyl cation (16), With the customary ellipsis of allowing a single valency structure to represent mesomeric systems. ... 

It is important to note that for methyl nitrenium ion the singlet state is not predicted at higher levels of theory to show a potential energy minimum. Rather this species is a transition structure that eliminates H2 without a barrier (Fig. 13.15). It seems likely that the difficulties encountered in attempting to study alkyl nitrenium ions might be traced to their propensity to rearrange or eliminate. 

Laser flash photolysis methods have also been applied to the study of nitrenium ion trapping rates and hfetimes. This method relies on short laser pulses to create a high transient concentration of the nitrenium ion, and fast detection technology to characterize its spectrum and lifetime The most frequently used detection method is fast UV-vis spectroscopy. This method has the advantage of high sensitivity, but provides very little specific information about the structure of the species being detected. More recently, time-resolved infrared (TRIR) and Raman spectroscopies have been used in conjunction with flash photolysis methods. These provide very detailed structural information, but suffer from lower detection sensitivity. 

The first nitrenium ion to be examined using any flash photolysis method was the 4-dimethylaminophenylnitrenium ion (131). However, the workers who carried out these experiments apparently did not consider this species to be a nitrenium ion. It was generated by pulsed Xe lamp photolysis from the corresponding azide (132, Fig. 13.64), and was detected through its absorption at 325 nm. As the resonance structure 131 implies, this nitrenium ion (or quinonediimine) is especially stable. In fact, its lifetime exceeds 100 ms at neutral pH, and it decays through hydrolysis of the C=N bond to give iminoquinone (133). 

A promising recent development in the study of nitrenium ions has been the introduction of time-resolved vibrational spectroscopy for their characterization. These methods are based on pulsed laser photolysis. However, they employ either time resolved IR (TRIR) or time-resolved resonance Raman (TRRR) spectroscopy as the mode of detection. While these detection techniques are inherently less sensitive than UV-vis absorption, they provide more detailed and readily interpretable spectral information. In fact, it is possible to directly calculate these spectra using relatively fast and inexpensive DFT and MP2 methods. Thus, spectra derived from experiment can be used to validate (or falsify) various computational treatments of nitrenium ion stmctures and reactivity. In contrast, UV-vis spectra do not lend themselves to detailed structural analysis and, moreover, calculating these spectra from first principles is still expensive and highly approximate. 

More recently, time-resolved vibrational spectroscopy has been applied to nitrenium ions. These techniques hold much promise for future research as they can provide more detailed structural information about nitrenium ions. In addition, the vibrational frequencies measured in this way can be used to assess the accuracy of theoretical calculations. 

The substituent effects calculated for A show that aromatic and vinylic jT-donors in the para-position have a stabilizing effect on the nitrenium ions that is much larger than is seen in Op. For example, Op for Me, MeO, and Ph are —0.31, —0.78, and —0.18, respectively, while A for 75y (Ar = 4-tolyl), 75cc (Ar = 4-MeOphenyl) and 75n (Ar = 4-biphenylyl) are 8,1 kcal/mol, 22.7 kcal/mol, and 19.3 kcal/mol, respectively. The calculations and experimental data show that a para-phenyl substituent is about as stabilizing for a nitrenium ion as is a para-methoxy substituent. This unusual stabilization is the major reason that correlations of logS vs. cr are so scattered for nitrenium ions. Substituent effects at N are relatively small. Replacement of NH by NAc destabilizes the ion toward hydration by 4.5 l.Okcal/mol. Based on the correlation line, at 20°C this amounts to a predicted increase in by a factor of 4 to 11 when NH is replaced by NAc. The experimentally observed range of 1.5 to 9.0 (Table 1) is very close to this prediction. These calculated substituent effects on the thermodynamics of hydration and the calculated geometries of nitrenium ions (discussed in another section) indicate that for most nitrenium ions the canonical structure II of Scheme 38 is dominant. ... 

In most cases the only isolated produet of N3 attack on a nitrenium ion is the orrho-substitution product 82. The para-product 81 has never been directly observed but its existenee can be inferred in a few cases because of unusual N3 adducts that have been isolated. The likely pathways for decomposition of 81, based on the structures of isolated products, are summarized in Scheme 45. 

One unusual aspect of these benzidine species is that the dications are less reactive toward solvent than are the monocations. This was not observed for the 2-fluorenyl and 4-biphenylyl nitrenium ions 75g and 75n and their conjugate acids 144g and 144n. The reason for this is not clear, but may be related to the fact that the two positive charges in 144qq and 144rr can be localized onto the two nitrogens on opposite ends of the structures. 

Recently Ford and co-workers performed calculations of the structures and relative stabilities of a series of 20 polycyclic nitrenium ions at the HF/6-31G(d) level.Except for symmetrical cases, all ions existed as distinct syn and anti isomers defined by the configuration of the N—H bond with respect to the unsymmetrical aryl group. The energies of configurational isomers differed by between 0.2 and 3.7 kcal/mol. Inversion barriers through a linear transition state were fairly constant in the range from... 

Reactions of nitrenium ions with DNA. Most of what is known about their reactions with DNA bases is derived from studies with monomeric bases. Some work with DNA oligomers has been reported, but tittle is known of the effects of DNA tertiary structure on these reactions. 

Nitrenium ions are isoelectronic to carbenes [177]. They contain a dicoordinated nitrogen atom formally with two valence electrons. The possible electronic structures of the parent nitrenium ion NHj are shown in Figure 7.9. On the basis of Hiickel MO theory one would expect that the lowest energy configuration, that is, the electronic ground... 

Generally amino acid conjugation is a detoxication reaction. However, amino acid conjugation with hydroxylamino groups (N-hydroxy) can lead to the formation of reactive nitrenium ions, as already discussed with sulfate conjugation and acetylation. For example, the conjugation of serine with N-hydroxy-4-aminoquinoline-l-oxide (Fig. 4.40 for structure) leads to such a reactive nitrenium ion. This requires the enzyme serine-tRNA synthetase. 

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