Invertomer separation

Figure 6. Analytical invertomer separation of l-chloro-2,2-dimethyIaziridine by complexation GC on NLCAM2 (0.133 molal in squalane) at 60°C. Column 100 m x 0.5 mm (i.d.) metallic nickel capillary. Carrier gas Nj (3.8 ml/min), split ratio 1 50 (Schnrig et al., 1979).

Generally, the inversion at nitrogen is rapid and invertomer pairs are not isolated. In a few rare cases, however, a high nitrogen inversion barrier renders the invertomers separable.31 This point will be discussed later in more detail. The kinetic aspects of the nitrone-olefin cycloaddition have been extensively investigated by Huisgen32 and by Boyle.33... 

In complexation gas chromatography, semipreparative separations of spiroketals (among them pheromones) have been reported. The preparative invertomer separation of l-chloro-2,2-dimethylaziri-dine permitted the determination of chiroptical data, absolute configuration and inversion barrier. Very large separation factors a were observed for saturated hydrocarbons (cis- and tra s-pinane, camphene) on a mixture of a-cyclodextrin in form-amide impreg/nated on celite. The preparative enantiomer separation of a-ionone on (18) and of all-trans-perhydrotriphenylene on (25) has been described. The large separation factors observed for the inhalational anesthetics enflurane, isoflurane, and desflurane on (18) allowed their enantiomer separation for subsequent biomedical trials and acquisition of chiroptical data. The continuous preparative enantiomer separation of enflurane and... 

NMR investigations in the diaziridine field also led to the problem of inversion stability at nitrogen. Further investigations paralleled those of oxaziridines NMR investigation in solution (67CB1178) was followed by preparative separation of invertomers and finally preparation of optically active individuals. 

Interestingly, both invertomers of the obtained M-chloroaziridines 16 were clearly observable in the H-NMR spectrum and they could even be separated by chromatography. The dehydrochlorination was investigated with a variety of bases however, the resulting yields were disappointingly low. Only for R = Ph, a yield of 39% of azirine 17 was obtained using DBU as the base, in all other cases the yields were lower [22]. Davis et al. [23] successfully applied the -elimination of the sulfinyl group in chiral non-racemic N-sulfinylaziridines (Scheme 9), whereby the eliminated sulfenate was trapped by an excess of methyl iodide, which facilitated the isolation of the desired product (18). 

Molecular modelling (AMI) indicated that the bridge hetero-atom separations in 137 were as follows N-N = 8A, N-0 = 4.6A, 0-0 = 2.7 A. In addition, the invertomer preference of the N-benzyl groups position them over the aromatic rings thereby ensuring that the lone pairs on the heteroatoms are concentrated within the cavity section of the molecule. 

Key Words Preparative-scale GC, enantiomeric separation, chiral stationary phases, SMB-GC, nitrogen invertomer, inhalation anesthetics, terpenoids, flavours,... 

The invertomers of the nitrogen pyramid 1-chloro-2,2-dimethylaziridine have been separated by enantioselective complexation GC on the chiral metal chelate nickel(II)-bis[(3-heptafluorobutanoyl)-( l.R>)-camphorate] (Ni-CAM2) in squalane (Schurig et al., 1979). The resolution of the chiral aziridine into two sharp peaks with a = 1.5 in 45 min at 60° C demonstrated the stereochemical integrity of the invertomers (cf. Figure 6). 

Figure 7. Semi-preparative-scale separation of the invertomers of l-chloro-2,2-dimethylaziridine by complexation GC on Ni-CAMj at 22°C and 1.5 bar N2 in 3 h at 22°C. Injected amount of racemate 6 fi (further experimental conditions cf. text). The (S)-enantiomer is eluted before the (it)-enantiomer on Ni-CAMj (Schurig and Leyrer, 1990).

Since barriers in simple amines are in the range 16-40 kJ mol-1, isolation of optical isomers is not possible. However, substitution and incorporation of N into strained rings raises the barrier and in some cases invertomers have been separated. For the heavier elements (P, As, Sb, Bi), the inversion barriers of EH3 and ER3 molecules are much higher. 

There is a retarded rate of inversion, compared with alkylaziridines, in certain benzoxazolinone-substituted aziridines . The inversion in JV-halogeno-aziridines is slow enough to permit separation of the two invertomers in the case of N-chloro-2-methylaziridine and 7-chloro-7-azabicyclo[4,l,0]heptane . 

The invertomers of (228) have been separated by gas chromatography on a column coated with optically active nickel(ii) bis-3-heptafluorobutanyl-(l/ )-camphorate in squalene. The chiral invertomers gave two distinct peaks, of intensity 1 1. 

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