The Control of the Nitrogen Inversion in Alkyl‐Substituted Diaziridines

Abstract

For the first time the nitrogen inversion barriers in 3,3-unsubstituted trans-diaziridines, such as 1,2-di-tert-butyldiaziridine (1) and 1,2-di-n-butyldiaziridine (2) were determined. Enantioselective stopped-flow multidimensional gas chromatography was used to investigate the enantiomerization barrier of 1 between 126.2 and 171.0 degrees C (DeltaG ++ gas (150.7 degrees C) = 135.8+/-0.2 kJ mol(-1), DeltaH++ gas = 116.1+/-2.5 kJ mol(-1), DeltaS ++ gas == -46+/-2 J K(-1) mol(-1)). The separation of the enantiomers has been achieved in presence of the chiral stationary phase (CSP) Chirasil-beta-Dex with a high separation factor (alpha = 1.44 at 80 degrees C). In a complementary approach, the enantiomerization barriers of 1,2-di-tert-butyldiaziridine (1), 1,2-di-n-butyldiaziridine (2), 1-n-butyl-3,3-dimethyldiaziridine (3), and 1,2,3,3-tetramethyldiaziridine (4) were determined for comparison by enantioselective dynamic chromatography (DGC) and computer simulation of the dynamic elution profiles. The enantiomerization barrier of 2 was shown to be the highest among the nonsterically hindered diaziridines studied so far, whereas 1 exhibited the highest value found for strained nitrogen-containing rings, that is, aziridines, diaziridines and oxaziridines.

Fast and precise access to enantiomerization rate constants in dynamic chromatography

“…52 The enantiomerization barriers in 3,3-unsubstituted diaziridines are of great interest because the barrier is increased due to the absence of 1,2-nonbonded interactions which destabilize the ground state. 53 In the course of these investigations, the mixed 1,2-substituted diaziridine 1-n-butyl-2-tert-butyldiaziridine was synthesized according to Scheme 2a. The statistical reaction mixture of n-butylamine and tert-butylamine leads to a mixture of ditert-butyldiaziridine (2.0%), 1-n-butyl-2-tert-butyldiaziridine (85.6%), and di-n-butyldiaziridine (12.4%).…”

The stereodynamics of 1,2‐dipropyldiaziridines

“…3,3-Unsubstituted diaziridines are of great interest because the barrier is increased due to the lack of 1,2-nonbonded interactions which destabilize the ground state. 27 These diaziridines were chosen, because increasing the steric demand by introduction of a methyl group at the a-C atom of the substituent is more effective for shorter than for longer alkyl groups without introducing further stereogenic centers, e.g., for sec-butyl substituents. Furthermore, it is expected that if the interconversion barrier depends on the steric hindrance of the substitutents in a distinct inversion process, the barrier of the heterosubstituted diaziridine 2 should be the average of the barriers of the homosubstituted diaziridines 1 and 2.…”

Three‐Membered Heterocycles. Structure and Reactivity

“…For N,N-dialkyl derivatives, this barrier is even higher. For the di-tbutyl variant, it has been calculated at 30 kcal mol À1 [715]. As a result, trans-N,Ndisubstituted diaziridines have been recognized as novel C 2 -symmetric compounds, and efforts have been made to elaborate methods for their resolution [716,717].…”