Ammonium nitrogen inversion

The barrier for the unique process observed in these zwitterionic complexes, the ammonium nitrogen inversion , was observed and measured by SIR, looking at transfer of magnetization between two C-methyl signals in the 13C NMR spectrum (Fig. 65). The free energy barrier at 360 K in nitrobenzene- solution was AG = 20.8 kcal mol-1, the same as for 105. 

Quaternary ammonium salts with asymmetric nitrogen atoms. Inversion of configuration is not possible because there is no lone pair to undergo nitrogen inversion. For example, the methyl ethyl isopropyl anilinium salts can be resolved into enantiomers. 

Fig. 63. Schematic representation of the topomerization of 103a via deprotonation at the ammonium nitrogen, followed by N-inversion and reprotonation, resulting in the interchange A B7, and B 5. A7.88 Reproduced with permission from the American Chemical Society.

The second process, inversion of the ammonium nitrogen, was also observed in 105, and had a barrier of 20.8 0.3 kcal mol-1, measured by the SIR technique at 360 K in nitrobenzene- solution. 

Ammonium salts cannot undergo nitrogen inversion because they do not have an unshared pair. Therefore, those quaternary ammonium salts with four different groups are chiral and can be resolved into separate (relatively stable) enantiomers ... 

Amines with three different substituents are potentially chiral because of the pseudotetrahedral arrangement of the three groups and the lone-pair electrons. Under normal conditions, however, these enantiomers are not separable because of the rapid inversion at the nitrogen center. As soon as the lone-pair electrons are fixed by the formation of quaternary ammonium salts, tertiary amide N-oxide, or any other fixed bonding, the inversion is prohibited, and consequently the enantiomers of chiral nitrogen compounds can be separated. 

Since k31/kl3 is equal to Kah, kl3, k3l and kH may be evaluated. Values of fen found depend markedly on the substitutents on the nitrogen ranging from 2.2 x 101 1 sec-1 for ammonium down to 2.7 x 109 sec 1 for dibenzylmethylammonium. The value of kH is also proportional to the inverse viscosity of the sulphuric acid—water mixtures used as solvent, over a five-fold range in viscosity. Grunwald and Ralph [79] interpret these results as meaning that kH measures the rate of diffusion of the water molecule into the bulk solvent. Water in the first... 

The lone pair is required for inversion Quaternary ammonium ions— ions with four bonds to nitrogen and hence no lone pair—do not invert. 

If one of the four groups attached to nitrogen is a lone pair, the enantiomers cannot be separated because they interconvert rapidly at room temperature. This rapid interconversion is called amine inversion (Figure 4.8). The lone pair is necessary for inversion quaternary ammonium ions—ions with four bonds to nitrogen and hence no lone pair—do not invert. One way to picture amine inversion is to think of an umbrella that turns inside out in a windstorm. 

Sample preparation Mix 2 mL serum with 10 irL 10 (xg/mL IS in MeOH, add 200 jxL concentrated ammonium hydroxide, add 5 mL dichloromethane, shake on a reciprocating shaker for 30 min, centrifuge at 730 g for 20 min. (If excessive emulsion is present, mix by inversion and centrifuge again.). Evaporate the organic layer to dryness in a silanized glass tube under a stream of nitrogen below 40°, reconstitute the residue with 80 pL mobile phase, vortex, inject a 25 pL aliquot. 

---