Nitrogen, inversion barrier

The fully saturated pyrazolidines have been utilized as models for the study of the nitrogen inversion of hydrazines. For instance, (75), a 2,3-diazabicyclo[2.2.1]heptene derivative, presents a consecutive inversion process at two nitrogen atoms with an activation barrier... 

Table 1 Barriers to Nitrogen Inversion in Substituted Aziridines ...

Although unsynunetrically substituted amines are chiral, the configuration is not stable because of rapid inversion at nitrogen. The activation energy for pyramidal inversion at phosphorus is much higher than at nitrogen, and many optically active phosphines have been prepared. The barrier to inversion is usually in the range of 30-3S kcal/mol so that enantiomerically pure phosphines are stable at room temperature but racemize by inversion at elevated tempeiatuies. Asymmetrically substituted tetracoordinate phosphorus compounds such as phosphonium salts and phosphine oxides are also chiral. Scheme 2.1 includes some examples of chiral phosphorus compounds. 

The barriers for nitrogen inversion in 1,3,4-oxadiazolidine derivatives have been determined by the introduction of chiral substituents on the nitrogen atoms and monitoring diastereomerization by NMR and by following enantiomer-ization by multidimensional gas chromatography <2000AGE2938>. 

In conclusion, the barrier of nitrogen inversion in cyclic nitrosoacetals is very high. This circumstance allows one to distinguish kinetic and thermodynamic... 

Table 3.28 The barriers of nitrogen inversion of BENA and related compounds determined with dynamic NMR...

SCHEME 1. Conformational map of the RcRn and RcSn diastereomers of /V-ethyl-iV-methyl-2-aminobutane (EMAB). Interconversions among conformers within dashed boxes are fast on the NMR time scale at 104 K. Those between dashed boxes occur via rotations about the methine carbon-nitrogen bond with barriers which are DNMR-visible. The interconversion between the solid boxes occurs via nitrogen inversion (disstereomeric interconversion). The values in parentheses are MM2-80 results. Reprinted with permission from Reference 71. Copyright (1988) American Chemical Society... 

In cyclic amines rigidity of the ring and a small angle between the C-N bonds characteristically result in a relatively high energy barrier to inversion of configuration at the nitrogen atom. The effect is most marked for aziridine derivatives, for which the kinetics of inversion processes are conveniently studied by variable-temperature NMR... 

Preliminary studies of nitrogen substituent inversion processes have been reported for several naphthalen-l,4-imine derivatives. The syn and anti invertomers of the A-chloroamine (117) equilibrate in solution to a mixture in proportion 3 2. The process can be followed kinetically by NMR spectroscopy starting from the pure anti compound the inversion is relatively slow ki = 2.6 x 10 sec at 23°), and the free-energy barrier to inversion is as high AF = 23.5 kcal mole ) as values found for inversion in aziridines. (A-Chloroaziridine derivatives, for which the energy barrier is even higher, have also been resolved into diastereoisomeric invertomers. )... 

The barrier to inversion at nitrogen in A-heteroatom-substituted hydroxamic esters should be greater than that found for hydroxamic esters or simple amides. However, it is likely to be substantially reduced in anomeric amides relative to amines since the planar transition state in which nitrogen is sp hybridized, can benefit from jr-overlap with the carbonyl (Figure 3b) and this has been verified experimenfally Rudchenko has measured an inversion barrier for A,A-dialkoxyureas af AG = 9-11 kcalmoH and fhose of acyclic dialkoxyamines fypicaUy af AG = 20-22 kcalmoH ... 

In amines, dialkoxyl subsfilufion resulls in much higher barriers to inversion fhan in alky famines a fad that has also been explained in terms of an electronegativity effect increased p-character in the a bonds results in more s-character for the electron pair on nitrogen. The planar-inversion transition state is therefore destabilized since, in it, the lone pair must develop pure p-character. This transition state is also destabilized by a six-electron anti-bonding interaction between heteroatom lone pairs and, additionally, the better anomeric overlap that is possible in sp rather than sp systems may also play a role (Figure 4) . These phenomena have also been rationalized theoretically ... 

The barrier to inversion at nitrogen was 3.5 kcalmol" at the B3LYP/6-31G level in line with that of the A-chloro model, 2b (2.5 kcalmol". Section III.B.l). 

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