High resolution mass spectrometry in molecular structure studies—VI: The fragmentation of amaryllis alkaloids in the crinine series. Compounds bearing a hydroxyl substituent at C-11 (and some 11-oxo derivatives)

High resolution mass spectral fragmentation patterns of Amaryllidaceae alkaloids in the crinine series bearing a substituent at C-11 have been investigated, as well as certain isotopically labeled derivatives. The substituent at C-11 governs almost entirely the fragmentation pattern of these bases due to the ability of the hydroxylic hydrogen atom to rearrange. In contrast to the bases lacking this hydrozyl substituent, stereochemistry exerts a profound influence on the fragmentation.     

Chemical ionization mass spectrometry studies—VII: Deuterium labeled decanes

CI mass spectra of the five isomeric vicinal d₂-decanes have been recorded using methane and d₄-methane as reagent gases. In contrast to earlier suggestions, we find that a large fraction of the alkyl fragment ions from n-decane are formed by elimination of olefins from the abundant [M – 1] ion. Only the C₉ and C₈ fragment ions are produced completely by a one-step reaction between the decanes and the methane reagent ions. Isotope exchange does not occur between the hydrocarbon and the reagent ions derived from d₄-methane but extensive scrambling of the deuterium label in the d₂-decanes does take place in the [M – 1] ion.     

High resolution mass spectrometry. Bufadienolides—II.

Complete low resolution mass spectra and high resolution data for selected important peaks are presented and discussed for a series of naturally occurring 14β, 15β-epoxybufadienolides (toad poisons) and their derivatives. The compounds examined were resibufogenin, marinobufagin, cinobufagin, desacetylcinobufagin, cinobufotalin, desacetylcinobufotalin and resibufagin, and the derivatives were 11α-hydroxyresibufogenin, 3β-acetoxymarinobufagin, 3-ketocinobufagin, 3β-acetoxy-16β-desacetylcinobufagin, 3β-acetoxy-16-ketocinobufagin, resibufaginol, 14α-artebufogenin and 3β-suberyloxyresibufogenin methyl ester. The relatively unsaturated 2-pyrone group of C-17β has been used as an integral label to distinguish (from elemental composition data) ions containing it from those arising in other parts of the molecule that do not, and the spectra are interpreted in terms of structural ‘ion types’.     

High resolution mass spectrometry in molecular studies. Part XVII. Evidence for ring contractions in molecular ions: The fragmentation of N-acetylmorpholine

In comparing N-acetylmorpholine to closely related systems, two major differences in fragmentation are observed. M-15 and M-43 fragments, although quite common to such systems, are unusual with respect to their genesis. Formation of the M-15 fragment by loss of C-3 instead of the anticipitated loss of C-2 or C-8 is evident from shifts in the spectra of deuterated analogs. The M-43 species arises from total loss of the N-acyl substituent rather than the usual two-step loss of ketene plus a ring hydrogen. These data are presented in support of mechanistic rationale involving radical induced ring contraction to a common intermediate molecular ion. Techniques of high resolution mass spectrometry and isotope labeling have been employed to substantiate certain mechanistic details.     

Heterocyclic studies—XXX: Application of mass spectrometry to the study of covalent hydration

Comparison of the mass spectra of 3,4-hydrated 4-trifluoromethylpteridine derivatives with those of corresponding anhydrous compounds shows that this technique can be used to deduce the position of covalent hydration in heterocyclic compounds. It is less easy to demonstrate the presence of added water molecules in 5,6,7,8-dihydrated derivatives of ethyl pteridine-4-carboxylates, but spectra run at low ionising voltages give the required information. Two hydrates (3,4-hydrates of 4-ethoxycarbonyl- and 4-trifluoromethyl-pteridine-2(1H)-thione) which are very much more thermally stable than usual are also discussed. Metastable peaks and accurate mass measurements support many of the postulated fragmentation pathways.     

High resolution mass spectrometry.—II Some substituted benzothiazoles

The mass spectra of nineteen substituted benzothiazoles have been recorded and the identity of the various ions in the mass spectra has been established by high resulution (accurate) mass measurement. Deuterium labelling has been used to elucidate the fragmentation processes of these compounds. The parent compound of the series, benzothiazole, exhibits the loss of hydrogen cyanide and carbon monosulphide from the parent ion as the most important decomposition pathways. The hydrogen atom concerned in the loss of hydrogen cyanide is shown to originate from the 2-position of benzothiazole, while in 2-substituted benzothiazoles, different mechanisms are apparent for the loss of hydrogen cyanide, and these are clarified by deuterium labelling. Some substituted benzothiazoles can lose sulphur from their molecular ions, a process which does not occur in benzothiazole itself. The substituted benzothiazoles undergo many other types of fragmentations, in some cases retaining the substituent, and in other cases losing it prior to collapse of the thiazole ring.     

Electron impact studies—LXV: Negative-ion mass spectrometry of functional groups 2-aryl-1,3-dithianes

The negative-ion mass spectra of 2-aryl-1,3-dithianes contain pronounced molecular anions together with fragment ions which are produced by both simple and complex cleavage reactions. These spectra contain further examples of specific hydrogen scrambling processes in negative ions. Nitroaryldithianes give intense negative-ion spectra, and that of the o-nitro derivative exhibits an unusual proximity effect. The fragmentation patterns have been examined using both ²H and ¹³C labelling and the metastable defocusing technique.     

Electron-impact studies—LI: Hydrogen randomization in the stilbene molecular ion

Hydrozen randomization precedes the formation of M^+· ? H· and M^+· ? CH₃· species from the stilbene molecular ion at 15 eV. The carbon atom involved in the M^+· ? CH₃· elimination originates randomly from the whole molecule. The [M ? 15] ion (m/e 165) in the spectra of stilbene and 9,10-dihydrophenanthrene is produced from a common ion.     

High resolution mass spectrometry—V: Cyclic esters of aliphatic α-hydroxy acids

The main fragmentation sequences of glycollide and its homologues are initiated by fission of a CO? O bond, leading to the formation of fragment ions of low, m/e, such as [R¹CO]⁺ and [CR¹R²CCO]⁺. When a hydrogen atom is present on a ring carbon atom, 1,3 hydrogen migration occurs to produce [CHR²OH]⁺. In case where a ring carbon atom carries an alkylchain ? C₂H₅, a McLafferty rearrangement occurs with the adjacent carbonyl group. When both ring carbon atoms are dimethyl substituted, a 1,4 hydrogen migration must be invoked to account for the observed fragmentation sequence.     

Electron impact mass spectrometry of nuphar alkaloids. II—Thiohemiaminals

The appearance of m/e 228 and 176 ions, useful in ascertaining the presence of the hemiaminal hydroxyl, are discussed for six thiaspirane-type hemiaminals isolated from Nuphar luteum and three epimeric pairs of α-thiohemiaminals derived from (–)-deoxynupharidine. Other groups of ions useful in ascertaining stereochemical differences of the sulfur moiety in α-thiohemiaminals are discussed for the same compounds. One such group of ions is comprised of 248, 246 and 231; a second is 192 and 191.     

Electron impact studies—LXVII. The mass spectra of alkyl-1,3-dithianes

The mass spectra of 1,3-dithiane, 2-methyl- and 2,2-dimethyl-1,3-dithiane have been studied by ²H labelling and metastable defocusing. The various molecular ions eliminate S₂H. to produce the ions [C₄H₇]⁺, [C₅H₉]⁺ and [C₆H₁₁]⁺ respectively, each of which scramble the hydrogens either before or accompanying further decomposition. Other processes are complex, but parallel those already reported for 2-aryl-1,3-dithianes.     

Electron-impact studies—L: Skeletal-rearrangement fragments in the mass spectra of diphenylpyrazoles and -isoxazoles

The mass spectra of all diphenylpyrazoles and -isoxazoles contain rearrangement peaks at m/e 165 [C₁₃H₉]⁺. In addition, the spectra of 3,5-diphenylisoxazoles contain peaks at m/e 180 [C₁₃H₁₀N]⁺, which are produced by specific phenyl migrations. The mechanisms of both rearrangement processes have been studied by deuterium labelling.     

Pharmacologically interesting compounds—I: High resolution mass spectra of phenothiazines

The mass spectra of twenty-six commercially available medicinal phenothiazines have been determined at high resolution. In each compound, the side chain attached to the 10-position of the phenothiazine ring contains nitrogen and fission of the C? C bond α to this nitrogen gives in most cases the base peak. Some of the compounds are also substituted at the 2-position and this substituent generally remains intact, though some substituents such as acetyl, propionyl, methoxyl and methylthio can undergo fragmentation. Fragmentations fall into three groups; those which give ions representing a part of the side chain; those which give ions representing the intact phenothiazine ring with part of the side chain attached; those which give ions representing a partially fragmented ring system.     

Reliability of veterinary drug residue confirmation: High resolution mass spectrometry versus tandem mass spectrometry

Confirmation of suspected residues has been a long time domain of tandem triple quadrupole mass spectrometry (QqQ). The currently most widely used confirmation strategy relies on the use of two selected reaction monitoring signals (SRM). The details of this confirmation procedure are described in detail in the Commission Decision 93/256/EC (CD). On the other hand, high resolution mass spectrometry (HRMS) is nowadays increasingly used for trace analysis. Yet its utility for confirmatory purposes has not been well explored and utilized, since established confirmation strategies like the CD do not yet include rules for modern HRMS technologies.     

The mass spectra of carboxylic acids—V: Carboxyl-carboxyl interaction in the fragmentation of some cycloalkene-1,2-dicarboxylic acids

The fragmentation mechanisms of the six isomeric cyclohexene-1,2-dicarboxylic acids are discussed. Only the 1-cyclohexene acid, by virtue of the major sequential losses of H₂O and CO₂ from the molecular ion, is readily distinguishable from its isomers, all of whose mass spectra are closely similar. In contrast to cis and trans cyclohexane-1,2-dicarboxylic acids, whose mass spectra were markedly different, the cis and trans cyclohexene-1,2-dicarboxylic acids fragment in a similar fashion. The mass spectra of 1-cyclopentene-1,2-dicarboxylic acid and 1-cyclobutene-1,2-dicarboxylic acid also exhibit a strong carboxyl-carboxyl interaction; the fragmentation behaviour of the 1-cyclopenteneacid is, however, more complex than that of the 1-cyclohexene and 1-cyclobutene acids.     

High resolution field desorption mass spectrometry—I: Nucleosides and nucleotides

The first complete high resolution (HR) field desorption (FD) mass spectra (MS) are presented and constitute a helpful tool in the structure elucidation of biologically significant compounds. This is especially relevant for the determination of the molecular weight of substances with very low volatilities which suffer from thermal decomposition when evaporated into the ion source. An additional advantage is the very small sample consumption (in the submicrogram range). Further improvements in the ion production method are the introduction of high temperature activated emitters and a specially designed micromanipulator for optimal adjustment of the field anodes. These enabled values of mass resolution between 15000 and 25000 (10% valley definition) to be achieved when vacuum evaporated Ag Br plates were used for photographic recording.     

Studies in mass spectrometry. I—Common intermediates in the fragmentation of isomeric compounds under electron-impact

In the particular case where a specific ion [c]^+· is generated with different internal energy, the variation of Z(E) = [(f)⁺]/[(c)^+·] vs energy of the electron beam is discussed in relation to the P(E_i) and k(E_i) functions which describe the decay process [c]^+· → [f]⁺. Qualitative application to seven isomeric hydrocarbons suggests that, among these isomers, two pairs might rearrange to a common intermediate before fragmentation occurs. It is found that in such cases the curves Z = f(E) for a given fragmentation are not superimposable but parallel, as suggested by theoretical considerations.