Ion–molecule reaction in the gas phase 4—Stereospecific nucleophilic substitution under ammonia chemical ionization conditions from diastereomeric methyl and benzyl ethers of 3-hydroxy steroids

The ammonia chemical ionization (CI/NH₄⁺]) mass spectra of a series of diastereomeric methyl and benzyl ethers derived from 3-hydroxy steroids (unsaturated in position 5 and saturated) have been studied. The adduct ions M+NH₄]⁺ and MH]⁺ and the substitution product ions M+NH₄? ROH]⁺ (thereafter called M_sH]⁺) are characterized by an inversion in their relative stabilites in relation to their initial configuration. M+NH₄]_α⁺ and MH]_α⁺ formed from the α-Δ⁵-steroid isomers are stabilized by the presence of a hydrogen bond which is not possible for the β-isomers. This stereochemical effect has also been observed in the mass analysed ion kinetic energy (MIKE) spectra of M+NH₄]⁺ and MH]⁺. The MIKE spectra of M_sH]⁺ indicate that those issued from the β-isomers are more stable than the one originating from the α-isomers. This behavior is also observed in the first field free region (HV scan spectra) for MH]⁺, M_sH]⁺ and M+NH₄]⁺ which are precursors of the ethylenic carbocations (base peak in the conventional CI/NH₄]⁺ spectra). Mechanisms, such as S_N1 and S_Ni, have been ruled out for the formation of M_sH]⁺, but instead the data support an S_N2 mechanism during the ion-molecule reaction between M+NH₄]⁺ and NH₃.