Mechanism and regioselectivity of electrophilic aromatic nitration in solution: the validity of the transition state approach

Abstract

The potential energy surfaces in gas phase and in aqueous solution for the nitration of benzene, chlorobenzene, and phenol have been elucidated with density functional theory at the M06-2X/6-311G(d,p) level combined with the polarizable continuum solvent model (PCM). Three reaction intermediates have been identified along both surfaces: the unoriented π-complex (I), the oriented reaction complex (II), and the σ-complex (III). In order to obtain quantitatively reliable results for positional selectivity and for modeling the expulsion of the proton, it is crucial to take solvent effects into consideration. The results are in agreement with Olah’s conclusion from over 40 years ago that the transition state leading to (II) is the rate-determining step in activated cases, while it is the one leading to (III) for deactivated cases. The simplified reactivity approach of using the free energy for the formation of (III) as a model of the rate-determining transition state has previously been shown to be very successful for halogenations, but problematic for nitrations. These observations are rationalized with the geometric and energetic resemblance, and lack of resemblance respectively, between (III) and the corresponding rate determining transition state. At this level of theory, neither the σ-complex (III) nor the reaction complex (II) can be used to accurately model the rate-determining transition state for nitrations.

Mechanism of Direct Electrophilic Aromatic Amination: an Electrophile is Found by Quantum‐Chemical Study

“…A comparison of the C−N distance in π‐complex, TS1, and σ‐complex shows that TS1 has a structure more similar to π‐complex. Thus, according to the Hammond postulate the direct amination has an earlier transition state than halogenations since halogenations show a closer structural similarity between the σ‐complex and corresponding transition state …”

“…The opposite relationship is observed between the PI and C4‐N α distance in TS1: with a decrease of PI the C4‐N α distance increases (Table ). Indeed, the more activating substituent is the earlier rate determining TS1 is observed as the reaction rate increases . Therefore, the structures and energies of rate determining TS1 of substrates with electron‐donating substituents is further away from the corresponding σ‐complexes.…”

“…At the same time, the opposite pattern is observed for TS1 with the C‐N α distance decreased in water (2.35 Å) and increased in gas phase (2.44 Å) leading to an increased free energy of TS1 in aqueous phase. The similar changes in energy were observed for the formation of the π‐complex in aqueous and gas phase in nitration . The rest of the PES profile is similar for the gas phase and water.…”

“…In contrast, when free energies of σ‐complex formation were used for the rate constants calculation, the correlation was much better with σ p + ( R 2 = 0.988, ρ =‐8.5) than with σ p ( R 2 = 0.908, ρ =‐10.7). The overall similar results were observed in, where authors correlated computed activation free energies and free energies of σ‐complex formation with σ m /σ p and σ m + /σ p + for nitration. For amination as well as for nitration the better correlations with σ p are consistent with early rate‐determining TS when the positive charge is located on electrophile and bond between nitrogen and aromatic carbon has not been formed.…”

Trichloroisocyanuric acid and NaNO2 mediated nitration of indoles under acid-free and Vilsmeier–Haack conditions: synthesis and kinetic study

“…Participation of the nitronium ion has been evidenced from the Raman spectroscopic studies of Kecki [11], which depicted a line at 1400 cm −1 in the Raman spectrum. In recent past quite a good number of workers focused their attention on quantum chemical studies to explore mechanism of nitration of aromatic compounds [12][13][14][15]. Review article published by Katrizky et al [16] provided excellent bibliography on the direct mono nitration of wide varieties of heterocyclic compounds like furans, pyrroles, thiophenes, pyrazoles, imidazoles, isoxazoles and thiazoles using nitric acid/trifluoroacetic anhydride as nitrating agent.…”