Generation of N,N-Di(4-bromophenyl)nitrenium Ion Under Acidic Conditions: Search for a Nitrenium Dication
The behavior of the N, N-di(4-bromophenyl)nitrenium ion under acidic aqueous conditions was examined via laser flash photolysis experiments. A long-lived species forms and can be assigned as the cation radical or the dication. This species is unreactive towards nucleophiles and reactive towards strong electron donors, consistent with a cation radical. Mechanistic analysis indicates its formation is through a separate pathway than that of the nitrenium ion, suggestive of a triplet mechanism.
Introduction<!>Scheme 1. Delocalization of positive charge in arylnitrenium ions<!>Methods<!>Synthesis: N-(4,4'-dibromodiphenylamino)-2,4,6-trimethylpyridinium tetrafluoroborate was<!>LFP Generation of Nitrenium
<p>Nitrenium ions are reactive intermediates characterized by a dicoordinate nitrogen atom having a lone pair of electrons and bearing a formal positive charge. These species are isoelectronic other reactive intermediates such as nitrenes, carbenes, and carbenium ions. [1][2][3] In general such species behave as strong electrophiles, reacting rapidly with weak nucleophiles such as water or 2 rearranging to form stable iminium ions. Due to their role in DNA damaging reactions, the arylnitrenium ions have been extensively characterized. [4][5][6][7][8] In general, it has been shown that there is significant delocalization of positive charge from the nitrenium ion center into the aromatic ring as illustrated in Scheme 1. For this reason, it is possible to form a nitrenium dication through protonation of the nitrogen lone pair.</p><!><p>Indeed McClelland et al. found evidence for such a species by laser flash photolysis (LFP) experiments on arylazides in acidic media. 9 In these studies, the dication was not directly detected. However, its formation was inferred on the basis of the pH dependence of nitrenium ion (i.e. the monocation) decay kinetics.</p><p>The diarylnitrenium ions (i.e. the series where both N substituents are aromatic rings) have been studied to a somewhat lesser extent than the monoaryls. As might be expected, the additional aromatic ring provides additional pi-donation to the nitrenium ion center, further stabilizing the nitrenium ions toward reactions with nucleophiles. For example, N,N-di(4-chlorophenyl)nitrenium ion reacts with methanol with a rate constant of 1.1 x 10 5 M -1 s -1 . 10 In contrast, a comparable monoaryl system, N-methyl-N-(4-chlorophenyl)nitrenium ion reacts methanol ca. 6000 fold faster (7.0 x 10 8 M -1 s -1 ). 11 The increased delocalization of positive charge in the diaryl series suggests that N-protonation might be even more favorable that it is in the monoaryl series.</p><p>Earlier studies 10,12  These ambiguities encouraged us to reexamine the long-lived species formed from in the photolysis of 1. Specifically, the formation and decay kinetics of both the nitrenium ion and the long lived species are studied by LFP as a function pH, added traps, etc. The results, described below, show: (1) Formation of the long-lived 720 nm peak increases at lower pH, but there is no corresponding acceleration in the decay of the singlet nitrenium ion, indicating that the 720 nm species is not formed from protonation of the singlet nitrenium ion. (2) The 720 nm species lives for >500 μs in water and does not react at an observable rate with any added nucleophiles. These experiments support the original assignment of the 720 nm signal to the radical cation, rather than the nitrenium dication. (3) Calculated electronic spectra (TD-DFT) are more consistent with the cation radical than the ground state of the dication. These observations lead us to re-affirm the original assignment. An alternative excited state pathway for formation of 3 is proposed.</p><!><p>General Procedures: UV-Vis spectra were collected on a Shimadzu UV-1800 spectrometer using UVProbe 2.43 software. Samples were scanned using a fast scanning speed and a sampling interval of 1.0 nm. Each sample was blanked with the solvent used in solvating the compound. Kinetic decay curves were fitted using MATLAB software. All 1 H NMR spectra were obtained on a Bruker 400 MHz instrument.</p><p>Laser Flash Photolysis Studies: Laser flash photolysis studies were conducted using a Nd:YAG laser (355 nm output) supplied by Continuum with pulses 4-6 ns in duration as the excitation source. The probe beam was a 350 W Xe arc lamp which passed through a monochromator to a PMT detector. Samples were prepared such that the absorption at 355 nm was between 1.0 and 2.0. When obtaining a full spectrum, a fresh supply of the substrate into the cuvette was attained by setting up a nitrogen purged flow cell which connects the cuvette to the stock solution via a double-headed needle. The photolyzate was then drained from the cuvette into a waste vessel. This setup prevents accumulation of photoproducts and avoids the depletion of the substrate throughout the duration of the experiment.</p><!><p>synthesized according to a literature procedure. 10</p><p>Calculations: Geometry optimizations and frequency calculations were carried out using the Gaussian09 suite of programs. 14 Structures were optimized using (U)M06-2X/6-311G++(d,p). To further verify this assignment, we also generated 3 by LFP using an alternate route.</p><!><p>Lusztyk and coworkers demonstrated that various arylamine cation radicals can be generated through photolysis of the corresponding N-nitrosamines under acidic conditions. 15 Using this methodology, cation radical 3 was generated as outlined in Scheme 3 and the resulting transient spectrum is shown in Figure 2. A broad signal at 700 nm is observed immediately following the laser pulse. As this decays, a longer-lived and sharper signal at 720 nm remains. This behavior is consistent with Lusztyk's report. The initial broad peak corresponds to the neutral radical 6. This species is replaced by 3 as the neutral radical acquires a proton. These experiments as well, as the earlier reports, show that the long-lived 720 nm signal is an excellent match for the cation radical 3. However, the observation that the 720 nm species forms in aqueous solution leaves unresolved the mechanism for its formation. The cation radical 3 would be derived from nitrenium ion 2 through a net H atom transfer (Scheme 4, Eq. 1). Water has a very high homolytic bond strength of 119.3 kcal/mol 16 and does not, generally, serve as a source of H atoms. Moreover, the observation that formation of the 720 nm species is enhanced under acidic conditions leaves open the possibility that this species may be the dication 4 derived from protonation of the nitrenium ion (Scheme 4, Eq. 2). In that case, the rate of protonation should increase with the concentration of hydronium ion, or decrease with pH. To test for this, LFP was used to determine the decay rate constant for 2 aqueous solution at varying values of pH. The results, diagrammed in Figure 3, show that this is not the case.</p><p>Specifically, there is a <20% variance in the decay rate constant for the nitrenium ion 2 over the pH range of 5.9 to 1.7. However, the yield of the long-lived 720 nm intermediate (evaluated by comparing the initial signal to the persistent signal at 720 nm, ΔA) increases substantially in over the range of pH 4 to pH 2. Regardless of the identity of the 720 nm, this experiment shows that it cannot arise from direct protonation of the singlet nitrenium ion 2. ΔA@720 nm 9 2X/6-311G++(d,p)), 14 and the electronic absorption spectra were calculated using TD-DFT. 14 The reported structures were all determined to be local minima on the PES through frequency calculations. Singlet-Triplet energy splittings include corrections for zero point vibrational energy (negative values indicate a singlet ground state). These results are summarized in Figure 4,which shows the geometries, and Table 1, which shows the energetic and structural predictions.  Calculated spectra for the nitrenium ion show good qualitative agreement with the experimental.</p><p>Two strong bands in the low wavelength and high wavelength visible region are predicted and observed. There are some quantitative disagreements, however. The low wavelength band in particular is predicted to be 50 nm lower than what is observed. An earlier calculation using a different functional (B3LYP) showed similar features. In that case the high wavelength feature showed the larger discrepancy. 10 Two of the calculated spectra show reasonable agreement with the long-lived intermediate. Both the cation radical 3 and the triplet state dication 4 are expected to have both UV as well as high wavelength visible absorption bands. However, the triplet state 4</p><p>is also predicted to lie about 7 kcal/mol above the singlet. In general, DFT calculated singlet-triplet energy splitting tend to overestimate the stability of triplets. Therefore, the calculated value is more likely to be less favorable to the singlet than the real value. The observed lifetime of >500 μs would not be consistent with an excited triplet dication.</p><p>Reactivity of the Long-Lived Intermediate. One significant challenge in evaluating the potential assignment of a nitrenium dication is the paucity of experimental data on their reactivity.</p><p>Intuitively, one would expect the increased positive charge density ought to make these species more reactive than the Consistent with this expectation, McClelland et al. inferred that the dication of 4-biphenlylylnitrenium ion reacts with water and other nucleophiles approximately 50 times faster than the corresponding monocations. 9 To confirm that this long-lived species is 3 as previously assigned, an electron donor was added in order to quench the signal. The parent amine 7 has an oxidation potential of +0.585 V 17 so in order for electron transfer to be exergonic, the electron donor must have a lower oxidation 11 potential. N,N-dimethylaniline (DMA), which has an oxidation potential of +0.53 V vs. SCE 18 , was selected and a transient absorption spectrum with the addition of DMA was obtained, as shown in Figure 5. Tetrabutylammonium chloride was also added in sufficient concentration to suppress any direct reaction between DMA and 2.</p><p>Addition of DMA accelerates the decay of the 720 nm species, and a new band at 470 nm grows in at approximately the same rate. The band at 470 nm agrees with the previously reported spectrum for cation radical of DMA. 19 Pseudo-first order analysis of the quenching of the longlived species by DMA provides a second order rate constant of 5.00 × 10 6 M -1 s -1 . This value is significantly slower than the diffusion limit. However, at the acidity necessary to produce the longlived species, the DMA trap is mainly in its non-reactive conjugate acid form (pKa =5.1). 20 Interestingly, as displayed in Figure 6, as the pH changes there is no change in the initial absorption at 450 nm where only 2 absorbs. This indicates that 3 is not formed from the same excited state intermediate that gives rise to 2.</p><p>-0.  (See SI). Future ultrafast studies of the early events in this process could help distinguish these possibilities. Finally, it is noted that the behavior reported here applies to photolysis of 1 in</p>