New aspects of electrophylic aromatic substitution mechanism: Computational model of nitration reaction

Nitration Agents

There are grounds for assumption that neutral molecule of nitric acid is inactive toward aromatic rings, and quantum calculations are in agreement with that: we have not found extremum points on potential energy surface (PES) corresponding to any chemical interaction. On the other hand, all investigated cations containing nitrogroup revealed affinity to aromatic π-system. There were considered: nitronium (NO2+), protonated nitric acid, nitracidium (H2NO3+), protonated methylnitrate (CH3O-NO-OH+), and protonated acetylnitrate as possible nitrating reagent in the media of acetic acid or anhydride (CH3COO-NO-OH+).

It is worth mentioning that existence of H+ or NO2+ cations in liquid phase is impossible: they are surrounded by dense solvate shell and have chemical bonds with the nearest molecule of solvent. Therefore, if we intend to build a model of nitration reaction on the basis of gas-phase calculations, we should take nitracidium or protonated acetylnitrate for nitration agent, the particles that could be considered the simplest solvate structures.

It is also important to note that the basicity of aromatic compounds is not less than that of nitric acid (see Table I), so under conditions of NO2+ formation there must exist protonation of aromatic substrate. Moreover, as we found out, protonated arene can react with neutral HNO3 (sort of inverse nitration reaction). (See subsequent section “Transition States.”) Not depending on real stability of nitronium,* we must mention that in the presence of water (and in common nitric mixture its concentration may be up to 10 mol/L) the equilibrium (2) must be inclined to the nitracidium formation. Similar influence will be showed by any substance less acidic than HNO3 solvent, for example, acetic acid.

Table I. Proton affinity of some nucleophils as enthalpy of reaction B + H+ ⇒ BH+ (kcal/mol).
RHF, gas−105−112−137−131−98−126−264
RHF, solv.73425375744544

To compare reactivity of different electrophils, the activation barriers of their reaction with benzene were calculated. The results are presented in Table II, along with electron affinities of electrophils.

Table II. Properties of some electrophils: activation energies of reaction with benzene (Ea), electron affinity (EA) as enthalpy of reaction E+ + e ⇒ E, RHF (kcal/mol).
Gas phaseLiquid phase
* Protonated acetyl nitrate appeared to be unstable in gas phase: it gave molecule of nitric acid and acetyl cation. On the other hand, under liquid-phase approximation, it was alright.

Nitronium is the most reactive among considered electrophils. This is because of its great electronegativity, large charge on N-atom, and its small size. This does not mean, however, that the other particles cannot be nitration reagents: their concentration can be much higher and they may be much easier to obtain, so the difference in heat of formation may cover the difference in activation energies.

Table II shows that gas-phase reaction and the one in liquid phase cardinally differs by the value of activation energy. This is a result of desolvation of electrophil caused by charge transfer from it to aromatic molecule and following charge delocalization.

As a whole, electronic structures of TSs of different electrophils resemble one another. Considering the uncertainness of the structure and stability of nitracidium and its derivatives, we decided to use NO2+ for a model nitration agent in further investigations of arene's reactivity.

* In Ref. [7] there were performed ab initio calculations of protonated nitric acid, and it was found that complex H2O•NO2+ is a more stable isomer (ΔΔHf = −17±2 kcal/mol, 20 kcal/mol below another isomer). Our semiempiric calculations gave that HNO3 protonation led to [HO-NO-OH]+ and [ H2O•NO2]+ was unstable toward dissociation. The same results in semiempiric calculations were obtained by Sandall [8].