Pyridinium-N -(2-pyridyl)aminides and related compounds: a theoretical study

Seven families of pyridinium-N -(heteroaryl)aminides, both azinyl and azolyl, have been studied. For each family, three structures have been considered, the "classical" and two radicals. The transition states corresponding to the rotation of the pyridinium and the heterocycle were calculated at the B3LYP/6-31G* level.


Introduction
2][13][14][15][16] Heterocyclic mesomeric betaines have been the subject of extensive investigation, mainly because of their 1,3-dipolar character, which allows them to take part in 1,3-dipolar cycloadditions with various dipolarophiles, thus generating novel five-membered aza heterocycles.As 1,4 dinucleophiles, heterobetaines can react with 1,2-dicarbonyl compounds to give a variety of azonia derivatives possessing a quaternary bridgehead nitrogen.They have also found widespread application in the synthesis of natural products and organic compounds of biological relevance.Amongst the rich reactivity of these compounds, Alvarez-Builla and coworkers discovered that that of azinium-N-ylides is controlled by the intramolecular hydrogenbond (HB) shown in Figure 1. 1,3,5,6For instance, alkylation occurs exclusively on the exocyclic nitrogen atom (the N -).However, when a radical is formed, the reactivity is modified and this was attributed to a new HB between the C • and the pyridinium C-H involving a conformational change. 7,9We will discuss in more detail their paper reporting X-ray data and AM1 calculations. 17We will use the term "neutral" for the closed-shell structures and "radical" for the open-shell ones, although the radicals are also neutral.
Due to our interest in HBs we decided to study these molecules in what concerns their influence on the conformational aspects and the rotation barriers.With this aim we have calculated all the compounds of Figure 2 as well as the transition states connecting them.We have previously studied theoretically pyrazolyl radicals. 18

Results and Discussion
The energies corresponding to Figure 2, both minima (all real frequencies) and transition states (only one imaginary frequency), are reported in Table 1.All the radicals structures with Cs symmetry present a 2 A' electronic configuration while the ones with C1 symmetry have a 2 A configuration.
We will discuss only the Erel values because those corrected with the ZPE, Erel(+ZPE) are almost identical and strictly proportional.The dihedral angles 1 (N1 + -N --C2'-C3') and 2 (C2'-N --N1 + -C2) are reported in Table 2.In their 1994 paper, Error!Bookmark not defined.Alvarez-Builla et al. reported the X-ray molecular structure of 1 (LESKEZ) 19 characterized by two dihedral angles, the one involving the C-N bond, 1 = 177.5ºand the one about the N-N bond, 2 = 65.7º,i.e. one ring is almost planar but the other is twisted.AM1 calculations were carried out rotating the 2 angle, finding that the planar structure (2 = 0º) is the most stable and the barrier to rotation about the N-N bond is 27 kJ mol -1 .The calculated dipole moments are 2.6 D (minimum) and 6.4 D (TS).They also reported that the C-H bond (C2-H) involved in the HB is elongated compared with other C-H bonds in 1. 17 Dipole moments.Our calculated dipole moments in the case of 1 are 2.51 D for the minimum (compare with 2.6 D) and 5.58 D for the TS corresponding to rotation about the N-N bond (compare with 6.4 D). 17 Minima.All the minima are planar, including 1, in agreement with the previous result. 17We have calculated two minima for the radicals, the N•••H and the C • •••H.In the case of the sixmembered rings, the structure with an HB with the lone pair (LP) of the nitrogen atom is more stable than that with an HB to the carbon atom radical by about 11-12 kJ mol -1 2/3, 5/6, 8/9.In pyrazole 11/12 and in 2H-1,2,3-triazole 17/18, the N lone-pair is preferred (8.9 kJ mol -1 and 8.2 kJ mol -1 , respectively).The replacement of an NH by an O atom (isoxazole and furazan) results in an important increase of these values, 20.5 and 22.2 kJ mol -1 , respectively.These effects are not only due to the strength of the hydrogen bonds, other factors, such as stereoelectronic ones, could contribute.

Barriers to the rotation about N-N and N-C bonds (transition states, TS).
We have considered two rotations, those about the single N-N and N-C bonds (Figure 3).The barrier calculated for the rotation about the N-N bond in 1 (33-34 kJ mol -1 ) is close to that calculated at the AM1 level (27 kJ mol -1 ). 17The rotations in neutral molecules are all degenerate (identical initial and final states).The fourteen barriers of Table 1   Protons H2 and H6 in 1 are magnetically equivalent (isochrones) because the barrier to the rotation about the N-N bond is low (about 33-34 kJ mol -1 ).

have been represented in
The two different TSs of Figure 6.
In the radicals, there are three barriers, two degenerate (the N-N) and two corresponding to an asymmetric process (the N-C).For the asymmetric one, we have used the barriers from the most stable to the less stable rotamer, see Figures 5 and 6.For instance, in the case of pyrimidine, we have used 22.7 kJ mol -1 for the degenerate N-N barrier 5-5 and 45.2 kJ mol -1 for the N-C barrier 5-6, resulting from 48.6 -12.1 values of Table 1. Figure 6 shows that both barriers are related and, as in the case of the neutral molecules, when one increases the other decreases, meaning that the partial double bond character of two single bonds (the N-N and the N-C) are related.

Molecular electrostatic potential (MEP).
We have calculated the MEP of the three structures of pyridinium-N-(2-pyridyl) aminides 1-3 (Figure 7).The radical formation results in an increment of the nucleophilicity of the aminide nitrogen; regarding the pyridine nitrogen, it slightly reduces its nucleophilicity in 2 while it almost doubles its value in 3.This variation in the electrostatic potential, with the observed changes in the conformational profile, could explain the reactivity differences between 1 and their radical counterparts, 2/3.Contrary to what was reported previously, 17 in our calculations the C-H bond involved in the HB interaction is always shorter (in average 0.002 Å) than the corresponding one that is not involved in this interaction.The topological analysis of the electron density shows in all cases an intramolecular HB critical point (Figure 8).The values of the electron density, bcp, and Laplacian,    bcp, at the intramolecular HB are typical of this kind of weak interactions. 20In previous reports, a linear and exponential relationship between bcp and the intermolecular distances has been shown. 21In the present case, the data are clustered based on the size of the ring attached to the pyridine one (Figure 9).Thus, the five membered ring derivatives show smaller bcp for a similar intermolecular distance than the one obtained in the six membered rings.No significant differences are obtained for the N   In conclusion, the present work on pyridinium-N-(heteroaryl)aminides provides a rationale for the design of new conjugated heterocyclic-N-aminides.The conformational preferences of the radicals and the different transition states have been calculated and some relationships between them found.The molecular electrostatic potential analysis can be used to explain the modification of the reactivity between closed-shell and open-shell structures.The topological analysis of the electron density of the N•••H and C • •••H hydrogen bonds shows that both are similar.
The analysis developed here (B3LYP/6-31G*) goes much farther (MEP, electron density) than the previous work carried out at the AM1 level and should be considered more reliable.Depending on the property that is desired to optimize, further experimental work should explore other six-or five-membered rings.

Computational Details
Calculations were carried out at the B3LYP/6-31G* level 22,23 (unrestricted for radicals) using the Gaussian 03 programs. 24Frequency calculations at the same level were carried out to verify that the structures correspond to energy minima (no imaginary frequencies) or to TS (only one imaginary frequency).
The analysis of the electron density of the systems has been carried out using the Morphy98 program, 25 and Morphy3 graphic interface 26 within the Atoms in Molecules (AIM) framework. 27

Figure 7 .
Figure 7. From left to right, MEPs at ±0.04 au of 1, 2 and 3.The values of the minima for each negative region are indicated.

1 2 3 Figure 8 .
Figure 8.Molecular graph based on the electron density.The bond and ring critical points are indicated as well as the bond paths.

Figure 9 .
Figure 9. Electron density at the bcp vs. the interatomic distances.The black symbols correspond to compounds 1-9 while the white ones to 10-21.The squares indicate the N•••H interactions while the triangles the C • •••H ones.

Table 3 .
Properties of the intramolecular HB: distances in Å and electron density and Laplacian in au