The electron impact and fast atom bombardment mass spectrometry of aziridines and their 2-chloroethylamine precursors

Abstract

A mass spectrometric method for the analysis of aziridines and their 2-chloroethylamine precursors is described. These compounds are characterized by their highly labile interconvertible nature. The capabilities of electron impact and fast atom bombardment (FAB) mass spectrometry as ionizaton techniques for structure confirmation studies were explored. A new technique using FAB mass spectrometry to distinguish between an aziridine and its open-chain precursor is described. INTRODUCTIONDuring an investigation of contraceptive compounds occurring in the shrub Salsola tuberculatiformis Botsch., an active fraction (S2), showing a single symmetrical peak in different high-performance liquid chromatography (HPLC) systems, was isolated in microquantities.' This fraction proved to be highly sensitive to light, heat, alkaline pH and air. Autocatalytic degradation and polymerization occurred very rapidly if appropriate steps were not taken. Decomposition in acidic aqueous medium led to the formation of I-(4-hydroxyphenyl)-2-(methylamino)ethanol (I, Fig. I), also called synephrine. This paper describes the utilization of electron impact (ET) and fast atom b~m b a r d m e n t~,~ (FAB) mass spectrometric techniques for the chemical investigation of S2, a number of structurally related synthetic aziridines and their 2-chloroethylamine precursors.Acetylation of S2 yielded a derivative which, although still labile, showed a reduced tendency to decompose in In an attempt to gain insight into the composition and chemical properties of this active fraction (S2), a series of eight model compounds (IVa-d, Va-d, Fig. 2) was synthesized, purified and the structural integrity of each confirmed by nuclear magnetic resonance (NMR). Compounds IVa and IVb were synthesized from l-phenyl-2-aminoethanol and l-phenyl-2-(methylamino)ethanol according to the method of AppeL7 Treatment of 1-phenyl-2-aminoethanol and l-phenyl-2-(methylamino)-ethanol in chloroform with gaseous hydrochloric acid yielded compounds Va and Vb. Compounds Vc and Vd were obtained from octopamine and synephrine by Mass spectra were recorded on a VG70-70E mass spectrometer equipped with a VG2035 data system. All samples were run under positive ion operating conditions. EI operating conditions were as follows: electron energy 70 eV; filament emission current, 100 FA; source temperature, varied between 80 and 200 OC; acceleration voltage, 4 kV. The magnetic analyser was scanned at a rate of 2 s per decade in the mass range 400-30 Da. Samples were introduced into the ion source using the standard VG heated direct-insertion probe.FAB mass spectra were recorded with an Ion Tech saddle-field gun' employing xenon9 as bombardment gas (8 kV, 1 mA). The mass spectrometer was operated at 6 kV and the magnetic analyser was scanned at a rate of 5 s per decade over the range 500-100 Da. Glycerol," obtained from Fluka, was employed as a matrix, however; 3-nitrobenzylalcohol" proved to be equally suitable. RESULTS A N D DISCUSSIONThe EI and FAB results of this study are summarized in Table ...

Biological activities of the shrub Salsola tuberculatiformis Botsch.: Contraceptive or stress alleviator?

“…(22) In addition, both ACTH and CBG concentrations were significantly (P < 0.05) lower than controls. The levels of the gonadotropins were also reduced during treatment but only the LH values were significantly lower (P < 0.05).…”

“…21) and the structure of the precursor and its aziridine confirmed by EI and FAB mass spectrometry. (16,22) Was compound A a good model for the unstable S2: did it defer oestrus in rats and inhibit P450c11?…”

“…(29) In addition, the administration of certain drugs, or the presence of certain exogenous compounds, may affect the transport and disposition of the endogenous steroids. (28,30) We chose initially to investigate CBG in an attempt to find a unifying mechanism of action that would reconcile the diverse effects, such as contraception in rats (22) and prolonged gestation in sheep, (5) of the biologically active phenyl aziridines. Rat plasma does not contain SHBG (31) and it has been shown in fetal sheep that the prepartum rise of cortisol does not result in negative feedback to the pituitary, and thus attenuation of the signal, because of a concomitant rise in CBG; (32) perturbation of this balance may therefore influence the timing of parturition.…”

Differentiation of the Aziridine Functionality from Related Functional Groups in Protonated Analytes by Using Selective Ion-Molecule Reactions Followed by Collision-Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer

“…This prevents the detection of the molecular radical cations and hence the determination of the molecular weights (M w ) of the analytes. 9 Tandem mass spectrometry (MS 2 ) based on collisionactivated dissociation (CAD) is a powerful method for the identification of many unknown ionized analytes in complex mixtures. 10,11 However, isomer differentiation is challenging as many ionized isomers fragment in a similar manner.…”

“…However, the EI method often causes extensive fragmentation to the molecular radical cations of the analytes, especially for aziridines, which produce [M – H] + ions instead of molecular radical cations upon EI. This prevents the detection of the molecular radical cations and hence the determination of the molecular weights ( M w ) of the analytes …”