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.

Keywords: Electrophilic aromatic substitution; Nitration; Quantum chemistry; Regioselectivity; Transition state.

Fig. 1

The putative mechanism for S_EAr nitrations

Fig. 2

Structures of stationary points in the gas phase nitration of benzene optimized at the M06-2X/6-311G(d,p) level. Bond lengths in Angstroms and angles in degrees. Adapted from [6] with permission from John Wiley & Sons, Inc., Copyright

Fig. 3

Structures of stationary points in the nitration of benzene in aqueous solution optimized at the M06-2X/6-311G(d,p) level. Bond lengths in Angstroms and angles in degrees. Adapted from [6] with permission from John Wiley & Sons, Inc., Copyright

Fig. 4

The free energies of the stationary points on the PES for the gas phase nitration of benzene computed at the M06-2X/6-311G(d,p) level. Included in italics is the corresponding point group symmetry at the different stationary points. Free energies without symmetry corrections are given in parentheses

Fig. 5

The free energies of the stationary points on the PES for the nitration of benzene in aqueous solution computed at the M06-2X/6-311G(d,p) level. Included in italics is the corresponding point group symmetry at the different stationary points. Free energies without symmetry corrections are given in parentheses

Fig. 6

The structure of the para isomer for the stationary points on the PES for nitration of chlorobenzene. Bond lengths in Angstroms and angles in degrees

Fig. 7

Standard free energies at the stationary points on the PES for the nitration of phenol in aqueous solution (1 M, 298.15 K). The species to the left of the gap are calculated with the bare PCM description. The three species to the right, indexed with “w” as in water, are calculated with PCM and one explicit water molecule coordinated to the structures. The energy for the (III_w) para isomer has been leveled with the corresponding para structure (III). Note that a C _2v point group symmetry was assumed for phenol (R) due to the near degeneracy of the ortho and meta sites with H directed toward or away from the site. The difference between the ortho TS1 for the different sites is, e.g., 0.16 kcal mol^-1

Fig. 8

Some para isomer structures for the nitration of phenol. The σ-complex, with and without an explicit water molecule, and the TS2, the expulsion of the proton. Bond lengths in Angstroms and angles in degrees

Fig. 9

Para isomers for the TS1 and σ-complex structures (III) for the chlorination of benzene