Stereodynamics of tetramezine

Abstract

The antidepressant drug tetramezine [1,2-bis-(3,3-dimethyldiaziridin-1-yl)ethane] consists of two bridged diaziridine moieties with four stereogenic nitrogen centers, which are stereolabile and, therefore, are prone to interconversion. The adjacent substituents at the nitrogen atoms of the diaziridines moieties exist only in an antiperiplanar conformation, which results in a coupled interconversion. Therefore, three stereoisomers exist (meso form and two enantiomeric forms), which epimerize when the diaziridine moieties are regarded as stereogenic units due to the coupled interconversion. Here, we have investigated the epimerization between the meso and enantiomeric forms by dynamic gas chromatography. Temperature-dependent measurements were performed, and reaction rate constants were determined using the unified equation of chromatography implemented in the software DCXplorer. The activation barriers of the epimerization were found to be ΔG(≠) = 100.7 kJ mol(-1) at 25°C and ΔG(≠) = 104.5 kJ mol(-1) at 37°C, respectively. The activation enthalpy and entropy were determined to be ΔH(≠) = 70.3 ± 0.4 kJ mol(-1) and ΔS(≠) = -102 ± 2 J mol(-1) K(-1) .

New Trends in Diaziridine Formation and Transformation (a Review)

“…Recently, experimental data were obtained for the structural determination of N,N-disubstituted diaziridine [22] and its trisubstituted form, which possesses an additional alkyl group at position 3 [23,24], bis-diaziridine [25], and bicyclic diaziridine [26] derivatives by the method of gas electron diffraction. Most diaziridine derivatives are liquids; thus, the recent experimental determination of its structures on the basis of X-ray diffraction studies [21,27] has only been performed in a few cases. Investigation of conformational and configurational changes in order to understand the effect of the interconversion barrier on the steric hindrance of the diaziridine substituent has also been conducted using dynamic gas chromatography [28][29][30].…”

6,6′-Dimethyl-1,1′,5,5′-tetraaza-6,6′-bi(bicyclo[3.1.0]hexane): synthesis and investigation of molecular structure by quantum-chemical calculations, NMR spectroscopy and X-ray diffraction analysis

“…The diaziridine derivatives are capable of direct action on the central nervous system, possessing various types of neurotropic activity [14][15][16][17][18][19][20]. Diaziridines appeared to be suitable objects for studying of the stereochemistry of the nitrogen atom due to the high stability of the two stereogenic pyramidal nitrogens [21][22][23]. Strained diaziridine ring is inclined to ring-expansion reactions resulting in various ve-to-eight-membered monoand bicyclic heterocyclic structures [24][25][26][27][28][29][30].…”

Chiral 1,2‐Dialkenyl Diaziridines: Synthesis, Enantioselective Separation, and Nitrogen Inversion Barriers

“…Herein we report the synthesis of 1,2-diaziridines, substituted with terminal alkenyl groups (allyl 11 to pentenyl) and the investigation of their stereodynamic properties compared to the wellknown alkyl diaziridines. [2][3][4]12 To determine the activation parameters ΔH ╪ and ΔS ╪ , temperature-dependent measurements using enantioselective dynamic gas chromatography (DGC) were performed, because the activation energy for the nitrogen inversion in diaziridines is usually well above 90 kJ mol À1 . 4,[13][14][15] In particular, the influence of the alkenyl chain length was investigated, which provides valuable data for designing novel chiral switchable structures.…”