Mass spectrometry and structures of ions of heterocyclic compounds activated by collision. 2. 2-Methylnitroindolizines

The principal pathways of the fragmentation of 2-methylnitroindolizines were investigated. The fragmentation and structures of the isomeric [M-OH]⁺ and [M-NO]⁺ ions formed in the fragmentation of these compounds were studied by the method of dissociative activation by collision (DAC). It was established that the stable [M-OH]⁺ ions formed in the fragmentation of the 1- and 3-nitro isomers as a result of the ortho effect have different structures and that their DAC spectra can be used to determine the position of the nitro group in the molecule.See [1] for Communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1631–1635, December, 1988.     

Mass-spectrometric study of 4-azaphenanthrene derivatives

The mass spectra of 15 compounds of the 4-azaphenanthrene series and their deutero analogs with bulky R substituents (R=-CCPh, -CH=CHPh, CHBr-CHBrPh,-CH=CHC₆H₄OCH₃-p, -COOH, -COOC₂H₅, and -CONHNH₂) in the ortho position relative to the nitrogen atom were studied. An intense [M-H]⁺ ion peak, the appearance of which is evidently due to a process involving cyclization of the carbon atom of the side chain with the nitrogen atom, is formed in the fragmentation of the styryl derivatives. The fragmentation of the compounds with a methyl group in the ortho position relative to the styryl grouping is accompanied by the formation of an intense [M-Ph]⁺ ion peak. An ortho effect of the carboxyl and carbethoxy groups adjacent to the methyl substituent is observed in the mass spectra of the investigated compounds. The data obtained make it possible to establish the structures of bulky substituents in the ortho position relative to the ring nitrogen atom and the position of the methyl group in the pyridine ring of monomethylated azaphenahthrenes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 659–665, May, 1979.     

Mass-spectrometric study of methyl-substituted azomethines of the 4-azafluorene series

The M⁺ and [M-H]⁺ ion peaks are the peaks of maximum intensity in the mass spectra of Schiff bases belonging to the 4-aza-9-fluorenylidenearylamine series. The dependence of the relative intensity of the [M-H]⁺ fragment on the structures of the I–XI molecules provides evidence for the possibility of the occurrence of rearrangement processes involving the formation of this ion. The formation of [M-CH₃]⁺, [M-HCN]⁺, [M-Ar]⁺, and [M-CNAr]⁺ ions is also characteristic for the fragmentation of the investigated compounds. It was found that, in contrast to other types of Schiff bases, the ejection of an HCN molecule during the mass-spectrometric fragmentation of the investigated compounds occurs without participation of the nitrogen atom of the azomethine group. The elimination of a CNAr particle by the molecular ions is a distinctive feature of the investigated series of Schiff bases.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 397–402, March, 1979.     

Mass-spectrometric study of physiologically active β-thiosemicarbazones of N-alkylisatins

The molecular ions of isatin (I) and N-methyl- (II) and N-ethylisatin (III) -thiosemicarbazones undergo fragmentation via many pathways with the elimination of NH₃, H₂S, CO, CH₂N₂, CHN₃, CH₂N₂S, CH₂NS, and CHNS particles; this is due to primary localization of the charge on the heteroatoms of the thiosemicarbazone residue. A previously unknown rearrangement, which consists in migration of an HS group to the -carhon atom of the heteroring with subsequent ejection of a CHN₃ fragment. The [M — CO]⁺ ions undergo fragmentation with the elimination of CH₂N₂S; in the case of II and III fragmentation is preceded by detachment of a hydrogen atom (II) or a methyl group (III) from the substituent attached to the ring nitrogen atom. The [M — CO, -H, -CH₂NS]⁺ (II) and [M — CO, -CH₃, -CH₂N₂S]⁺ (III) ions undergo fragmentation with the ejection of HCN in two ways through both the ring nitrogen atom and the thiosemicarbazone residue. Schemes for the principal pathways of fragmentation and rearrangements are presented. The compositions of the ions were confirmed by the high-resolution mass spectra and the mass spectra of the N-deuteroalkyl derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–79, January, 1979.     

Mass Spectra of New Heterocycles. XVII. Main Fragmentation Routes of Molecular Ions of 4-Alkoxy-5-amino-3-methylthiophene-2-carbonitriles under Electron and Chemical Ionization

For the first time decomposition was investigated of 4-alkoxy-5-amino-3-methylthiophene-2-carbonitriles under the conditions of electronic (70 eV) and chemical (reagent gas methane) ionization. At the electronic ionization the compounds under study [except for 4-(1-ethoxyethoxy) and 4-(ferrocenylmethoxy) derivatives] form stable molecular ions that decompose mainly by the cleavage of an alkyl radical from the alkoxy-substituent. Further fragmentation of the arising ion [M–Alk]⁺ depends on the substituent nature in the amino group. In the mass spectrum of 4-(ferrocenylmethoxy)-substituted thiophene peaks of the ion [FcCH₂]⁺ and its fragmentation products prevail. In the mass spectra of chemical ionization predominant peaks belong to ions M^+·, [M + H]⁺ and [M + C₂H₅]⁺, and fragment ions are absent.     

Mass spectrometric study of methyl-substituted 4-azaphenanthrenes and their nitration products

The mass spectral behavior of five derivatives of the 4-azaphenanthrene series — 1,3-dimethyl-(I), 2,3-dimethyl-(II), 1,2,3,-trimethyl-(III), 1,2,3-trimethyl-8-nitro-(IV), and 1,3-dimethyl-6,7-dinitro-4-azaphenanthrene (V) — was studied. The stabilities of the molecular ions with respect to gragmentation (W_M) are higher by a factor of two or more for the methyl-substituted I–III than for nitro derivatives IV and V. The intensity of the [M-H]⁺ ion peak in the mass spectra of I–V does not depend on the number of methyl groups but only on their positions: the presence of a CH₃ group in the 2 position leads to an [M-H]⁺ ion that is 1.5 times more intense than when there is a methyl group in the 1 position. The molecular ions of I–V do not eliminate HCN molecules; this constitutes evidence for the absence of randomization of their methyl groups. The presence of a CH₃ substituent in the 1 or 2 position does not affect the intensity of the [M-CH₃]⁺ ion peaks, while the simultaneous presence of CH₃ groups attached to the C₁ and C₂ atoms increases the intensity of the [M-CH₃]⁺ fragment peak by a factor of two. In the mass spectra of nitro derivatives IV and V, [M-O]⁺, [M-OH]⁺, [M-NO]⁺, and [M-NO₂]⁺ fragments are observed in the first step of the fragmentation of the M⁺ ion, whereas the [M-CO]⁺ ion peak characteristic for the dissociative ionization of 1-nitronaphthalene is also observed for 8-nitro-substituted IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1365–1369, October, 1977.     

Electron impact ionization mass spectrometry and tandem mass spectrometry of phenylalkylpyridazines

The mass spectrometric fragmentation behaviour of pyridazine and four monosubstituted derivatives containing a pbenylalkyl side-chain (3- and 4-benizylpyridazine, 3- and 4-(2-pbenylethyl)pyridazine) was investigated. In the electron impact ionization mess spectra of the 3-substituted compounds abundant [M – H]⁺ peaks are observed. This allows a clear distinction between 3- and 4-substituted pyridazines, as the spectra of the latter isomers show only very weak [M – H]⁺ signals. The stability of [M – H]⁺ ions derived from 3-alkylpyridazines (deduced from only the very low abundance of further fragment ions) gives strong evidence for a cyclic structure of these ions. One fragmentation pathway typical of the parent pyridazine, the [M - N₂] fragmentation, was not detectable with any of the phenylalkylpyridazines investigated. Instead, loss of HCN, H₃CN⁺ and N²H⁺ was observed. An interesting fragmentation, observed with 3-(2-phenylethyl)pyridazine, is the loss of ⁺CH₃ from the molecular ion and also from the [M – H]⁺ ion.     

Mass-spectrometric behavior of some cyano-substituted 4-(β-chloroethylmercapto)-sym-triazines

Intense [M-Cl]⁺ and [M-CT₂=CCNCl]⁺ ion peaks are characteristic for the mass spectra of 4-(-chloro--cyanoethylmercapto)-sym-triazines. The introduction of monoalkylamino groups into the 2 and 6 positions of the heteroring does not lead to the development of [M-HCl]⁺ ion peaks in the mass spectra or to a change in the characteristic fragmentation pathways.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1268–1270, September, 1982.     

Tetraplatinum Cluster Complexes

The tetranuclear platinum cluster complexes [Pt₄(-CO)₃(-dppm)₃(PPh₃)]²⁺ and [Pt₄(-H)(-CO)₂(-dppm)₃(PPh₃)]⁺ have been prepared by cluster expansion. They have butterfly structures and are fluxional.     

Cyclization processes in the fragmentation of the molecular ions of N-(aza-9-fluorenylidene)amines

The dissociative ionization of 17 Schiff bases obtained from 2(4)-azafluorenones and linear benzo-1,4-diazafluorenone was investigated. The intensities of the [M-H]⁺ and [M-CH₃]¹ ion peaks depend on the structures of the ketone and imine parts of the molecules and are determined by the possibility of the occurrence of cyclization processes with the participation of their structural elements. The fragmentation of the investigated azomethines is also accompanied by the elimination of an NR particle and a hydrocarbon R radical by the molecular ions. This process takes place most easily when a cyclohexyl substituent is present in the imine fragment. In contrast to previously investigated azomethines, the loss of an HCN molecule by the M⁺ ion occurs without participation of the exocyclic nitrogen atom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 102–109, January, 1981.     

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.     

Application of mass spectrometry in structural and stereochemical investigations

The mechanism of the process M⁺→(M-CO)⁺ during fragmentation, under the influence of electron impact, of some bicyclic amines with a nodal nitrogen atom and containing an oxo group in various positions of the bridged system is discussed. Data on the ionization potentials and low-voltage mass spectra and from high-resolution mass spectrometry are used.     

The terfenadine/β-cyclodextrin inclusion complex

Terfenatine (TFN) is a very hydrophobic antiallergic drug. It exists in three polymorphic and two solvated forms and is practically insoluble in water. These properties make a pharmaceutical formulation with acceptable biopharmaceutical characteristics difficult to prepare. Inclusion complexation with -cyclodextrin (CD) may eliminate such problems. The properties of the TFN/CD system have been studied in liquid, gaseous and solid phases by¹H and¹³C NMR spectroscopy, powder X-ray diffractometry, differential scanning calorimetry and fast atom bombardment mass spectrometry. The solubility phase diagram was also recorded. In solution and in the gaseous phase the 11 complex prevails, whereas a 12 TFN/CD complex has been isolated by precipitation from homogeneous solution.     

Mass-spectrometric study of 3,9-diazabicyclo- and 3,9-oxaazabicylo[3.3.1]nonanes

The mass spectra of substituted 3,9-diazabicyclo- and 3,9-oxaazabicyclo[3.3.1]-nonanes were studied as a function of competitive distribution of the charge between the N₃ and N₉ and O₃ and N₉ atoms and the properties of the substituents attached to the heteroatoms. It is shown that a characteristic peculiarity of the fragmentation of 3,9-diazabicyclo[3.3.1]nonanes is fragmentation of the molecular ion with an open structure that is formed by cleavage of the C₁-C₂ bond. The formation of an amine fragment with retention of the bicyclic structure with an exocyclic double bond attached to the quaternary N₉ atom is characteristic for 3,9-oxaazabicyclo[3.3.1]nonanes. It is shown that this sort of behavior of the investigated compounds is determined by their structures and the properties of the heteroatoms in the saturated bicyclic systems.Communication 12 from the series Application of mass spectrometry in structural and stereochemical studies. See [1] for Communication 11.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 229–235, February, 1981.     

Structure and mechanism of fragmentation of [C2H5O]+

The decomposition reactions of [C₂H₅O]⁺ ions produced by dissociative electron-impact ionization of 2-propanol have been studied, using ¹³C and deuterium labeling coupled with metastable intensity studies. In addition, the fragmentation reactions following protonation of appropriately labeled acetaldehydes and ethylene oxides with [H₃]⁺ or [D₃]⁺ have been investigated. In both studies particular attention has been paid to the reactions leading to [CHO]⁺, [C₂H₃]⁺ and [H₃O]⁺. In both the electron-impact-induced reactions and the chemical ionization systems the fragmentation of [C₂H₅O]⁺ to both [H₃O]⁺ and [C₂H₃]⁺ proceeds by a single mechanism. For each case the reaction involves a mechanism in which the hydrogen originally bonded to oxygen is retained in the oxygen containing fragment while the four hydrogens originally bonded to carbon become indistinguishable. The fragmentation of [C₂H₅O]⁺ to produce [CHO]⁺ proceeds by a number of mechanisms. The lowest energy route involves complete retention of the α carbon and hydrogen while a higher energy route proceeds by a mechanism in which the carbons and the attached hydrogens become indistinguishable. A third distinct mechanism, observed in the electron-impact spectra only, proceeds with retention of the hydroxylic hydrogen in the product ion. Detailed fragmentation mechanisms are proposed to explain the results. It is suggested that the [C₂H₅O]⁺ ions formed by protonation of acetaldehyde or ionization of 2-propanol are produced initially with the structure [CH₃CH?\documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm O}\limits^ + $\end{document}H] (a), but isomerize to [CH₂?CH? \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm O}\limits^ + $\end{document}H₂] (e) prior to decomposition to [C₂H₃]⁺ or [H₃O]⁺. The results indicate that the isomerization a → e does not proceed directly, possibly because it is symmetry forbidden, but by two consecutive [1,2] hydrogen shifts. A more general study of the electron-impact mass spectrum of 2-propanol has been made and the fragmentation reactions proceeding from the molecular ion have been identified.     

Laser induced fission of C60 with kinetic energy release

A neutral C₆₀ fullerene beam is ionised by 308 nm laser pulses. For each cluster sizeC _n ⁺ , 0n60 of the typical bimodal mass distributions known from the literature [1] velocity distributions have been determined by a time of flight method. A consistent interpretation of the measured mean velocities is obtained when binary fission of the parent molecule is assumed to be responsible for the fragmentation patterns, the total kinetic energy release being 0.45±0.1 eV independent of fragment mass and of laser fluence.     

Arylation of α-Substituted Diethyl Methylphosphonates with π-Complexes of Haloarenes

Nucleophilic aromatic substitution of halogen in neutral and cationic -complexes of haloarenes ⁶-(ArF)Cr(CO)₃ and [⁶-(ArHlg)FeCp]⁺[PF₆]^- (Hlg = F, Cl) by carbanions derived from -substituted diethyl methylphosphonates [CHZP(O)(OEt)₂]^- (Z = CN, COOEt), generated in situ by the action of Cs₂CO₃, leads to formation of the corresponding arylmethylphosphonate complexes in 78-88% yield. The reaction of the complexes [⁶-{ArCHZP(O)(OEt)₂}FeCp]⁺ [PF₆]^- with 1,10-phenanthroline in acetonitrile on exposure to daylight yields 32-44% of the free diethyl arylmethylphosphonates.     

Binuclear copper complexes with non-steroidal anti-inflammatory drugs as studied by electrospray ionization mass spectrometry

The solutions containing one of the copper salts (CuCl₂, Cu(ClO₄)₂, Cu(NO₃)₂, and CuSO₄) and one of the non-steroidal anti-inflammatory drugs (NSAIDs, ibuprofen, ketoprofen or naproxen) were analyzed by electrospray ionization mass spectrometry. Three of the salts, namely CuCl₂, Cu(ClO₄)₂ and Cu(NO₃)₂, yielded binuclear complexes of drug:metal stoichiometry 1:2. Existence of the complexes of such stoichiometry has not been earlier observed. For copper(II) chloride the complexes (ions of the type [M-HCOOH+Cu₂Cl]⁺ and [M+Cu₂Cl]⁺, M stands for the drug molecule) were formed in the gas phase. When copper(II) perchlorate or copper(II) nitrate was used, the observed binuclear copper complexes (ions of the type [M-H+Cu₂(ClO₄)₂+CH₃OH]⁺, [M-H+Cu₂(ClO₄)₂]⁺ and [M-H+Cu₂(NO₃)₂+CH₃OH]⁺, [M-H+Cu₂(NO₃)₂]⁺) were observed at low cone voltage, thus these complexes must have already existed in the solution analysed. Therefore, such complexes may also exist under physiological conditions.      

A comparison of electrospray tandem mass spectra of some sialic acid derivatives: Ion trap and high resolution QqToF mass spectrometers

Using O-acetyl-N-acyl derivatives of O-methyl sialoside methyl esters, it was shown that an ion trap and a hybrid analyzer (linear quadrupole–time-of-flight analyzer, reflectron) give comparable, though not identical secondary mass spectra for the [M + Na]⁺ and [M + K]⁺ ions. A parallel use of an ion trap and a hybrid QqToF instrument gives information about the fragmentation pathways of ions of sialic acid derivatives under collisional activation. In this case, the sequence of fragmentation may be established using an ion trap, whereas a QqToF instrument offers a possibility of revealing the elemental composition of fragment ions quickly and unequivocally.     

Tetrazoles. 9. Acid-base properties of 5-substituted tetrazoles

The basicities of series of 5-R-tetrazoles in aqueous solutions of sulfuric acid were studied by UV and PMR spectroscopy. The pK_BH ⁺ values of these compound correlate with the _p substituent constants. The transmission factor of the p-phenylene ring (' = 0.23) was calculated from the ratio of the reaction constants for protonation of substituted 5-phenyltetrazoles and 5-R-tetrazoles. A linear dependence between the pK_a values and the pK_BH ⁺ values of 5-substituted tetrazoles was established.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 559–562, April, 1981.