Translational energy release and stereochemistry of steroids. IX-The mechanism of the elimination of water from metastable ions in epimeric 3-hydroxy steroids of the 5β-series

The mechanism of water elimination from metastable molecular and [M ? CH₃˙]⁺ ions, as well as from ions deprived of ring D, in epimeric 3-hydroxy steroids of the 5β-series has been elucidated by deuterium labelling, by the measurements of the translational energy released during loss of water, and by collision-induced decomposition mass-analysed ion kinetic energy spectrometry. It was found that the dehydration of the metastable molecular ion in 3α-hydroxy steroids of the 5β-series occurs mostly regiospecifically as an elimination of the 3α-hydroxyl together with the 9α-hydrogen atom. The ring A in the molecular ion has to flip to the boat conformation to make this reaction possible. In the metastable molecular ion of 3β-hydroxy steroids of the 5β-series a different dehydration mechanism operates, with very little participation of the 9α-hydrogen atom. The mechanisms of water loss from metastable [M ? CH₃˙]⁺ ions and from ions deprived of ring D differ from that of the molecular ion.     

Translational energy release and stereochemistry of steroids 4—Epimeric 3-keto and 3-hydroxy steroids

The translational energy, T, released during CH₃˙ loss from the molecular ions of epimeric steroid ketones and from both molecular and [M-H₂O]⁺˙ ions of epimeric alcohols of the androstane, pregnane and cholestane series, differing in the mode of the A/B ring junction, has been measured. These data provide a simple and rapid method for identifying the configuration of the epimeric centres. Of the compounds studied, it is found in 3-hydroxy steroids that the 5β-isomers release the smaller amounts of translational energy for CH₃˙ loss. In most of the 3-keto steroids investigated, the opposite is found, i.e. the larger T values are observed for the 5β-isomers. Exceptions occur when further keto groups are introduced at the 11- or 17-positions. A small range of epimeric pairs of 17-hydroxy, 17-keto and 4-keto steroids have also been studied, the 5β-isomer giving the lower T value in each case. The importance of hydroxy and keto groups at the various sites within the steroid structure in determining the T values is discussed.     

Translational energy release and stereochemistry of steroids. VII—the loss of angular methyl groups after the dehydration of molecular ions of cholesterol and related C(5)-unsaturated 3β-hydroxy steroids

The translational energy, T, released during the loss of the angular 18- and 19-methyl groups both from metastable molecular ions and metastable [M ? H₂O]⁺ and [M ? 2H₂O]⁺ ions, in C(5)-unsaturated mono-and di-hydroxy steroids, as well as in their 19-nor and deuterated analogues bearing the label in the 19-methyl group, has been measured. It was found that, while the T values for the 19-CH₃ loss, following the dehydration of the molecular ions, are increased substantially when compared to those for the same loss from the molecular ions, the T values for the 18-CH₃ loss are increased much more moderately. Nevertheless, the amounts of translational energy released in the [M ? H₂O]⁺˙ ? 18-CH₃˙ and [M ? 2 H₂O]⁺˙ ? 18-CH₃˙ transitions are still higher than those found for the respective 19-methyl loss, in accordance with the general rule established recently.     

Kinetic energy release in metastable ions from β-keto esters

The kinetic energy release, T, in metastable ion transitions accompanying the main fragmentation reaction by electron impact has been determined for methyl-, ethyl- and propyl-pivaloyl acetates. The measurements have been made using a MAT 311 mass spectrometer with inverse Nier–Johnson geometry, by high voltage and mass-analysed ion kinetic energy methods. The peak width at 50% height has been used in the calculations. The T values and the shape of the metastable peaks are correlated to reaction types and to the alcohol radical.     

Translational energy release and stereochemistry of steroids. 14. Epimeric dihydroxy steroids of the androstane series

The stereochemistry of dihydroxy steroids, both the mode of the A/B ring junctions and the configuration of OH groups, may be determined from translational energy (T50%) measurements for the loss of a CH.3 radical, from the ratios of metastable-ion peak heights to those of the main beam (determined for the dehydration reactions), and by comparing unimolecular and collision-induced, mass-analysed ion kinetic energy spectra of the new main beam of [M-H2O]+ ions (i.e. those formed via dehydration of metastable molecular ions of epimeric hydroxy steroids in the first field-free region of a double-focusing mass spectrometer.     

Translational energy release and stereochemistry of steroids. XI—Determination of the configuration of α,β-unsaturated 3-keto steroid alcohols with the hydroxyl group in rings C and D

The elimination of water from metastable molecular ions of epimeric hydroxy steroids of the Δ⁴-3-keto series containing a hydroxyl group in the conformationally rigid rings C and D has been studied. The measurement of translational energy released during the loss of water and collision-induced decomposition (CID) mass-analysed ion kinetic energy (MIKE) spectrometry were the techniques used. It was found that it is possible to determine the configuration of the hydroxy steroids of this series on the basis of the CID MIKE spectra of [M ? H₂O]^+˙ ions formed by dehydration of metastable molecular ions in the first field-free region of a reversed geometry double-focusing mass spectrometer.     

Translational energy release and stereochemistry of steroids 6—Contribution of the 18- and 19-methyl groups to the translational energy release for the angular methyl loss in unsaturated steroids

The translational energy, T, released during angular methyl loss from the molecular ions of unsaturated steriod hydrocarbons and alcohols, containing the double bond in the position allylic to either the 19-CH₃ or 18-CH₃ group, has been measured. The different contributions of the two angular methyl groups to the overall T value for the [M]⁺˙→[M? CH₃]⁺ reaction are discussed.     

Microwave-assisted synthesis of α-hydroxy ketone and α-diketone and pyrazine derivatives from α-halo and α,α′-dibromo ketone

A novel reaction of α-halo ketone (α-bromo and α-chloro ketone) with irradiation under microwave gave the corresponding α-hydroxyketone and pyrazine derivative in good yields. In the case of α,α′-dibromo ketone, α-diketone was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxyketone, α-diketone, α-chloro ketone and pyrazine derivative.     

Kinetic energy release during CO loss by rearrangement of α-benzoylcarbenium ions

Primary α-benzoylcarbenium ions (a) and tertiary α-benzoyldimethylcarbenium ions (b) are obtained by chemical ionization of ω-hydroxyacetophenone and its dimethyl derivative, respectively. Both α-acylcarbenium ions decompose by a rearrangement reaction and subsequent loss of a CO molecule. The kinetic energy released during this process by metastable ions a and b has been determined under different experimental conditions. The kinetic energy released during the CO elimination from the tertiary α-benzoyldimethylcarbenium ions b is independent of the experimental conditions and gives rise to dish-topped peaks with T₅₀=440±20 meV in the MIKE spectra of b. In contrast to this the kinetic energy releases and the peak-shapes in the MIKE spectra of the primary α-benzoylcarbenium ion a varies with the experimental conditions. The mechanism of this rearrangement reaction is discussed, and it is shown by a MNDO calculation of the heats of formation of the relevant ions that the different characteristics of the kinetic energy release during the fragmentation of primary and tertiary carbenium ions can be attributed to different types of reaction energy profiles.     

Mass spectra of trimethylsilyl ethers of some Δ5-3β-hydroxy C 19 steroids

The mass spectra (20 eV electron energy) of a wide range of %Δ⁵-3β-hydroxy C₁₉ steroid TMS ethers have been examined with the aid of high-resolution mass measurements, together with deuterium and oxygen-18 labelling data. The validity of many previously proposed fragmentation modes has been confirmed. A number of ions regarded as diagnostic have been shown to be less specific than had been formerly supposed. Several novel fragmentations have been observed and investigated.     

A kinetic study of the oxidation of α-hydroxy acids and α-hydroxy ketones by potassium bromate

The oxidation of α-hydroxy acids and α-hydroxy ketones by Br(V) follows the rate-law However, the former reaction exhibits a second-order dependence on hydrogen ion concentration while the latter reaction has a third-order dependence. A mechanism involving a slow formation of a bromate ester of the α-hydroxy acid followed by a fast decomposition is proposed. A rate-determining formation of a bromate ester from the conjugate acid of benzoin, followed by a rapid decomposition of the bromate ester, explains the kinetic data for the oxidation of benzoin.     

Mass spectra of esters of α-hydroxy and α-methoxy acids

The most abundant fragment produced by electron bombardment of esters of the type R¹R²C(OR³)CO₂R⁴ is the R¹R²C = \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm O}\limits^{{\rm + } \cdot } $\end{document}R³ ion. Methyl glycollate (R¹ = R² = R³ = H, R⁴ = Me) eliminates the HCO˙ radical by a complex rearrangement involving the methylenic hydrogen atoms. The methyl and ethyl esters of methoxyacetic acid (R¹ = R² = H, R³ = Me, R⁴ = Me or Et) eliminate formaldehyde by the McLafferty rearrangement.     

Enantioselective synthesis of β,β-dialkyl α-hydroxy γ-butyrolactones

An ephedrine-derived morpholine dione is employed in the synthesis of chiral alkylidene morpholinones that are efficiently converted to β-substituted α,γ-dihydroxy butyramides, precursors of the corresponding butyrolactones. Enantioselective synthesis of a spiro analog of pantolactone as well as a naturally occurring pantolactone homolog is achieved with this protocol.     

Destabilized carbenium ions: α-imidoyl carbenium ions and the electron impact mass spectra of α-haloaldimines and α-haloketimines

A series of α-chloro- and α-bromoketimines compounds (1-9) with different substituents at the α-position and at the imino group has been investigated by electron impact mass spectrometry as possible precursors of the correspondingly substituted α-imidoyl carbenium ion, an important class of destabilized carbenium ions. The main fragmentation of the molecular ions of compounds, 1-9 in the ion source corresponds to an α-cleavage at the imino group; however, fragment ions are also formed by loss of the α-halo substituent. These fragment ions correspond at least formally to α-imidoyl carbenium ions. Their further reactions in dependence on the type of substituents at the imino group and at the α-C atom, were studied by mass-analysed ion kinetic energy and collisional activation mass spectrometry. The results agree with the initial formation of destabilized α-imidoyl carbenium ions but indicate an easy rearrangement of these ions in the presence of suitable alkyl substituents by 1,2- and 1,4-hydrogen shifts to more stable isomers.