## 2 Results and Discussion  
For all of the calculations presented in this work we used the PQS program package from Parallel Quantum Solutions together with the associated graphical user interface, PQSMol[12, 13]. Figure 1 depicts schematically the various amination reactions examined (as previously noted, the majority from the Malykhin group [7, 8, 9, 10]). Since all of the reactions _are_ animations, we have made an important modification to our standard calculational approach: instead of using the fluoride ion as a generic attacking nucleophile we specifically use NH\({}_{2}^{-}\). The use of the actual nucleophile instead of the fluoride ion as a possible extension to the basic model was mentioned in our last paper [2], and it just seemed dogmatic to us to use fluorine when the substituting group was known to be NH\({}_{2}\) in every case. Figure 1: Amination reactions in liquid ammonia. The use of \(\mathrm{NH_{2}^{-}}\) as the attacking nucleophile brings both advantages and disadvantages compared to \(\mathrm{F^{-}}\). One advantage of using the single-atom fluoride ion as a generic attacking nucleophile is that there are no additional conformational issues in the resulting Meisenheimer complex, greatly simplifying the calculations. On the other hand it is known that most substituents to an aromatic ring  
Figure 1: _Cont._  
direct para as far as replacement of fluorine is concerned, with any preferable ortho substitution nearly always resulting from direct interaction between the attacking nucleophile and the substituent, an interaction that cannot be modeled using fluorine. If we want to properly take into account interactions between an existing (already substituted) amino group and an attacking nucleophile, especially ortho to the existing amino substituent, then it seems pretty clear that the attacking nucleophile has to be represented more realistically, and so for these amination reactions we used NH2-. The conformational issue is more problematic than might at first be thought. For example, consider toluene (Scheme 1a and b). This is known to have C\({}_{\text{s}}\) symmetry and its vibrational spectrum can be fully analyzed under this point group [14]. Given C\({}_{\text{s}}\) symmetry, there are two possible configurations of the methyl group--as shown in (a) and (b) --in which the symmetry plane is either perpendicular to, or in the plane of, the aromatic ring, respectively, bisecting a methyl HCH angle. The ground state geometry actually conforms to (a) with (b) being the transition state for methyl rotation. At room temperature the methyl group is essentially a free rotor with a 3-fold torsional potential. The amino group is conformationally similar to the methyl group with one of the C-H bonds replaced by a lone pair, although the two N-H bonds in aniline are nowhere near as \"bent\" out of the plane of the aromatic ring as are the methyl C-H bonds in toluene. Aniline also has C\({}_{\text{s}}\) symmetry in its ground state, with the lone pair occupying the position of the symmetry-unique C-H bond of the methyl group in toluene, _i.e._, perpendicular to the benzene ring (Scheme 1c). **Scheme 1. ** Conformational preferences in toluene and aniline. Now as soon as you add, e.g., a second methyl group to toluene, the conformational issues increase significantly. Not only do you have the conformation of the new methyl group to consider, but the local three-fold symmetry of the original methyl group no longer holds globally and the three methyl hydrogen atoms are no longer equivalent. More to the point for this work, the same thing applies of course to the amino group. We have no desire to carry out an exhaustive conformational analysis each time we calculate the energy of a given Meisenheimer complex. We have found that the following tactics when constructing the initial starting geometry of a Meisenheimer complex increases the likelihood of optimizing to the global or a near-global minimum:  
1.