Nitrogen inversion, amines

As in the case of the MM2 force field, parameterization of MM3 for amines was based mainly on experimental data with occasional references to ab initio calculations, mainly to evaluate relative conformational energies and derive appropriate torsional parameters. As mentioned above, one notable difference between the two force fields is the removal of lp on sp3 nitrogens from MM3. This simplifies the treatment of vibrational spectra and allows for a realistic treatment of nitrogen inversion which could not be handled by MM2. As usual with MM3, parameterization was aimed at reproducing a variety of molecular properties such as structure, steric energy, dipole moments, moments of inertia, heat of formation and vibrational spectra. A complete list of MM3 parameters for amines is provided in Reference 6. 

Six-membered rings containing one nitrogen atom resemble cyclohexanes in their geometry, and the stereochemical dependence of substituent effects is often similar. However, there is a complication involving nitrogen inversion of neutral amines which results in different orientations of the lone pair with respect to the ring621 for such effects on chemical shifts see Section 4.1.1.1. and on /H C and 2/HH values see Section 4.1.1.2. 

Amines with three different substituents and an unshared pair of electrons have enantiomers. However, in most cases an NRR R"-type amine cannot be resolved. The amine undergoes a very rapid nitrogen inversion similar to that for a C undergoing an 5 2 reaction (Fig. 18-2). 

It is interesting to compare tert-butylbenzyl methyl amine (35) with the tetrahedral intermediate 36 derived from N-benzyl-N-methylacetamide which has a similar degree of substitution. The rotation barrier for the (CH3)3C — N bond and the nitrogen inversion barrier in 35 have been found identical and estimated at 6.2 kcal/mol (30). The higher value of 8.0 kcal/mol for the intermediate 36 must be a consequence of the double-bond character of the C —N bond (nitrogen atom has one secondary electronic effect (n-o )). 

Nitrogen inversion interconverts the two enantiomers of a simple chiral amine. The transition state is a planar, sp2 hybrid structure with the lone pair in a p orbital. 

Amines whose chirality stems from the presence of asymmetric carbon atoms. Most chiral amines fall into this group. Nitrogen inversion is irrelevant because nitrogen is not the chirality center. For example, butan-2-amine can be resolved into enantiomers because the 2-butyl group is chiral. 

In a number of cases, these two types of interconversion may be brought about as well by rotation about bonds, e.g. rotation about the (X,Y,Z)-N single bonds or the X=N double bond. This situation holds, for instance, in acyclic amines (methylamine, hydroxylamine. ..) and in imines. Furthermore, nitrogen inversion may in some cases occur in the same molecule together with ring inversion, for instance, in piperidine. It will thus sometimes be necessary to distinguish between internal... 

Dielectric relaxation measurements on some amines (aniline, N,N-di-methylaniline, benzidine. ..) display two relaxation times a longer one (of the order of 20—30.10-12 sec) attributed to overall molecular reorientation, and a shorter one (of the order of 1.10-12 sec) which may be interpreted as arising from an intramolecular process and has been attributed to nitrogen inversion 19-aa>, although this attribution is not unequivocal (rotation about the N—C bond may also contribute to the observed relaxation). 

Table 4. Activation parameters for pyramidal nitrogen inversion from NMR data Four and five membered cyclic amines and derivativesa)... 

In aromatic amines, the partial double bond character of the C-N bond will tend to enhance the rotation barrier, while the inversion is found to be reduced, as compared to aliphatic amines. For example, the rotational barrier in IV-methylaniline is just above 7 kcal/mol, while the nitrogen inversion barrier is 1.6 kcal/mol [88]. 

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