Mass spectra of sterically crowded trialkylsilyl derivatives of nucleosides

The electron impact mass spectra of tert-butyldimethylsilyl-, cyclo-tetramethylene-tert-butylsilyl and cyclo-tetramethylene-isopropylsilyl- ether derivatives of ribo- and 2′-deoxyribonucleosides are described in detail. The interpretation of fragmentation pathways of full and mixed derivatives was aided by metastable ion decomposition studies, precise mass and deuterium labelling measurements, and spectra of mixed derivatives containing the ‘passive’ (in these spectra) trimethylsilyl group. The sterically crowded silyl groups have a powerful fragmentation directing effect. Elimination of a bulky radical, R˙ (tert-butyl or isopropyl), from the molecular ion produces the siliconium ion [M? R]⁺, which is the precursor for most of the other prominent ions in the spectra. These arise from ‘siliconium ion rearrangements’ resulting from the interaction of the positively charged siliconium ion center with electron dense regions (i.e. oxygens) in the molecule, to form cyclic silyloxonium ions which subsequently decompose. Since the interacting oxygen and silicon must be sterically accessible, the fragment ion types and their abundances are very dependent upon structure. Consequently, [M? R]⁺ ions formed from 2′, 3′ or 5′-O-silyl groups give rise to different sets of daughter ions which, for the most part, are not found, or have very low abundances, in the mass spectra of underivatized or trimethylsilylated nucleosides. Detailed information on sugar and base moieties and isomeric substitution is readily obtained.     

Electron-impact mass spectrometry of Nuphar alkaloids

Principal peaks in the mass spectra of deoxynupharidine are accounted for on the basis of high resolution mass spectrometry and peak shifts in the mass spectra of deoxynupharidine-4-d₁ and deoxynupharidine-6β, 7β-d₂. Cleavage of the quinolizidine ring system of deoxynupharidine occurs predominantly in ring A, giving m/e 136, 107, 98, 94 and 81. The origins of the family of ions [M — alkyl]⁺ and m/e 178 are considered. A comparative survey is made of the occurrence of these ions, and others, in the mass spectra of piperidine, quinolizidine and thiospirane types of Nuphar alkaloids. Attention is directed toions useful in distinguishing structural types.     

Structural characterization of 1,3,4-thiadiazolo[3,2-a][1,3,5]triazines by electron impact mass spectrometry

The electron-impact-induced fragmentation of eleven 1,3,4-thiadiazolo[3,2-a][1,3,5]triazines was investigated with the aid of exact mass measurements, B/E and B²/E linked scans, and deuterated compounds. The dominating breakdown process in the electron impact mass spectra of 2-substituted 6-phenyl-1,3,4-thiadiazolo[3,2-a]-[1,3,5]triazine-5,7-diones (1–5) is a retro-Diels-Alder reaction. This process gives rise to the base peak, whereas the molecular ions are of very low intensity. In the mass spectra of 2-substituted 7-methylthio-1,3,4-thiadiazolo-[3,2-a][1,3,5]triazine-5-ones (6–11) in which this fragmentation cannot occur because of the two conjugated double bonds in the triazine ring, the molecular ions are very intense. The mass spectral data permits an unequivocal structure assignment to these compounds, which are otherwise difficult to characterize.     

Mass spectrometry of trialkylsilyl and acyl derivatives of 2′-deoxynucleosides

The electron impact mass spectra of monosilyl and mixed acyl-silyl derivatives of 2′-deoxynucleosides are described in detail. (Silyl = tert-butyldimethylsilyl, cyclo-tetramethylene-isopropylsilyl, or cyclo-tetramethylene-tert-butylsilyl; acyl = acetyl or trifluoroacetyl.) The interpretation of the fragmentation pathways was aided by metastable ion decomposition studies, precise mass and deuterium labelling measurements. Mass spectrally, the acyl substituents are mostly ‘passive’ and have (with possibly one exception) little fragmentation directing capability. In contrast, the silyl groups have powerful fragmentation directing properties. Elimination of the bulky alkyl radical R^˙ (tert-butyl or isopropyl) from the molecular ion produces the siliconium ion, [M–R]⁺, which is the precursor for most of the other prominent ions in the spectra. These arise from ‘siliconium ion rearrangements’ resulting from the interaction of the positively charged siliconium ion centre with the electron dense regions (i.e. oxygens) in the molecule, to form cyclic silyloxonium ions which subsequently decompose. Since the interacting oxygen and silicon must be sterically accessible, the fragment ion types and their abundances are very dependent upon structure. Consequently, [M–R]⁺ ions formed from 3′- or 5′-O-silyl groups give rise to different sets of daughter ions which, for the most part, are not found, or have very low abundances, in the mass spectra of underivatized or trimethylsilylated nucleosides. Detailed information on sugar and base moieties and isomeric substitution is readily obtained.     

A new procedure for the cyclization of 2-indole- and 3-indolecarbohydrazones to 5H-pyridazino[4,5-b]indole derivatives

A new procedure for the cyclization of 2-indolecarbohydrazones (5) to 1,2,3,4-tetrahydro-4-oxo-5H-pyridazino[4,5-b]indoles (6) and for the cyclization of 3-indolecarbohydrazones (7) to 1-oxo-1,2,3,4-tetrahydro-5H-pyridazino[4,5-b]indoles (8 and 9) is described. The hydrazones (5 or 7) were treated with an acyl halide (acetyl or benzoyl chlorides) and triethylamine in ethyl acetate of chloroform as solvents to give the compounds 6 (20–70%) from the compounds 5 , and the compounds 8 (20–60%) from the compounds 7 . Through refluxing with ethanol-hydrochloric acid the compounds 8a-8f selectively separate the acetyl group on N⁵ to give the respective compounds, 9a-9f. The ir and ¹H-nmr spectra of all the compounds 5, 6, 7, 8 and 9 and the uv, mass and ¹³C-nmr spectra of the compounds 7h, 7i, 8h and 8i are discussed.     

Fast-atom bombardment mass spectrometric studies of trisubstituted 3a,4,5,11-tetrahydro- 1,2,4-oxadiazolo[5,4-d][1,5]benzothiazepines

The fragmentation pathways of nineteen 1,3a,5-trisubstituted 3a,4,5,11-tetrahydro- 1,2,4-oxadiazolo[5,4-d][1,5]benzothiazepines have been studied with the aid of mass-analyzed ion kinetic energy spectrometry and exact mass measurements using fast-atom bombardment ionization. All compounds show a tendency to eliminate a neutral propene, or substituted or unsubstituted styrene, from the thiazepine ring to yield 1,2,4-oxadiazolo[5,4-b][1,3]benzothiazole ions, and further undergo reverse 1,3-dipolar cycloadditions to give benzothiazole ions. The formation of stable conjugated fused tetracyclic systems, substituted 1,2,4-oxadiazolo[5,4-f]phenanthridine ions, was also observed. Copyright © 1999 John Wiley & Sons, Ltd.     

The elimination of metal(I) hydride in the mass spectra of some metal(II) compounds

Metal(I) hydrides are eliminated as neutral species in the electron impact ionization mass spectra of copper(II) and palladium(II) complexes of ethylene-N,N′-3-benzoylprop-2-en-2-amine. Deuterium labelling shows that the hydrogen atom of the metal(I) hydride is derived predominantly from the ethylene bridge both for ion source reactions and for metastable ion transitions. Evidence supporting the proposed rationalization for elimination of metal(I) hydride is provided by the observation of an analogous reaction in the mass spectrum of (ethylene-N,N′-salicylaldiminato)copper(II). The mass spectrum of ethylene-d₄-N,N′-3-benzoylprop-2-en-2-amine shows an unusual rearrangement to give [C₇H₅D₂]⁺ ions involving a formal phenyl-to-methylene transfer.     

Mass Spectral fragmentation patterns of heterocycles. V . Electron impact promoted mass spectral fragmentation of indolo[1,7-ab][1]benzazepine and Some of its Derivatives

The fragmentation patterns of 1,2,6,7-tetrahydroindolo[1,7-ab][l]benzazepin-1-one ( 1 ), 6,7-dihydroindolo-[1,7-ab][l]benzazepine ( 2 ) and indolo[1,7-ab][1]benzazepine ( 3 ) on electron impact have been examined. Loss of carbon monoxide to form the base peak at m/e 207 and loss of CHO radical to give m/e 206 consititute the major fragmentation pathways for 1. The moleclar ions ( M ⁺) are abundant for each of the compounds; observed as the second most intense peak for 1 (85% relative intensity) and the base peaks for 2 and 3 . The spectrum of 2 is characterized by intense M-1 and M-2 ions and by the presence of a M-15 ion (m/e 204) of moderate intensity (11.4%). In all other respects the spectra of 2 and 3 are strikingly similar. The M-15 ion from 2 , assigned the heteroaromatic pyrroloacridinium structure, is also formed in the spectrum of 1. A second heteroaromatic ion at m/e 191, common to the spectra of 1 , 2 and 3 , is believed to have the pyrrolocarbazol-ium structure. Metastable ion transitions and exact mass measurements support most of the proposed fragmentation pathways and structural assignments.     

Fast atom bombardment mass spectrometry of some alkoxv- and chloro-silanes

The positive and negative FAB mass spectra of a series of alkoxy- and chloro-silanes X_m(CH₃)₃-_mSi(CH₂)_nR [m = 1 or 3, n = 3, 10 or 17, X = Cl or OMe or OEt, R = Me, NH₂, glycidoxy, COOMe, NHCO(CH₂)₇COOMe or NHCO(CH₂)₁₀CH₂OAc] were recorded in NBA and NPOE matrices. The chlorosilanes underwent rapid hydrolysis into silanols which condense to form siloxanes, the process being complete in NBA and partial in NPOE, yielding siloxane-based fragment ions in the positive spectra and silyloxyanions in the negative spectra. The alkoxysilanes were more resistant to hydrolysis, affording abundant [MH – HX]⁺ ions (X = OMe or OEt) in their positive FAB spectra and moderate to high intensity [M – H]^? ions in the negative mode, the latter undergoing characteristic sequential loss of C₂H₄, EtOH and C₂H₄. Significant variations were observed in the positive spectra of all the silanes with change of matrix.     

1,2,4-Triazino[4,3-c]- and [2,3-c]quinazolines

This paper describes the reactions of 2-o-aminophenyl-1,4,5,6-tetrahydro-1-methyl-1,2,4-triazine with a variety of reagents to give substituted 1,2,4-triazino[4,3-c]quinazolines or 1,2,4-triazino[2,3-c]quinazolines. Certain representative compounds of these two new heterocyclic systems were characterized by the tlc, ir, nmr, mass spectra, and identified by unequivacol synthesis.     

Mass spectrometry of heterocyclic compounds. V—Substituent effects on the fragmentation pathways of 3,5-diphenyl-1,2,4-oxadiazole derivatives

The 70 eV mass spectra of a number of derivatives of 3,5-diphenul-1,2,4-oxadiazole substituted either in the 5-phenyl (fifteen) or in the 3-phenyl (four) position, have been studied using exact mass measurements and metastable determinations by the defocusing technique. The substituent effects on the heterocyclic cleavage are not very important for electron-withdrawing and weak electron-donating groups. The main cleavage is the formal retro 1,3-dipolar cycloaddition with the positive charge retained by the C₇H₅NO (orYC₇H₄NO in the case of the 3-substituted derivatives) fragment specifically containing the 3-phenyl, as oreviously observed for 3,5-diphenyl-1,2,4-oxadiazole using labelling experiments. Two other minor primary processes leading to benzoyl and nitrile ions, both containing the 5-phenyl, become important in the case of the electron-donating substituted compounds. Correlation of the abundance of these fragmednts and of the molecular ions with σ⁺ (para) Brown constants is discussed. Proximity effets are shown by some ortho derivatives.     

Intramolecular aromatic substitution reactions in substituted N,N-dimethylthiobenzamide ions

The molecular ions of N,N-dimethylthiobenzamide and its ortho substituted derivatives (substituents CH₃, Cl, Br, I) lose a hydrogen atom and/or the ortho substituent. The mechanism of this process has been studied by measurements of the ionization energies, appearance energies of the product ions m/z 164 and the kinetic energy release during this process. The structure of the product ions m/z 164 and relevant reference ions have been investigated by mass analysed ion kinetic energy spectra, B/E linked scan spectra and collision induced decompositions. The results show clearly the formation of two different kinds of product ions m/z 164 depending on the substituent lost. Type a ions are formed by loss of a H atom or the CH₃ substituent and correspond to protonated 3,4-benzo-N-methylpyroline-2-thione. The formation of these ions occurs by a hydrogen rearrangement followed by an intramolecular substitution via a 5-membered cyclic intermediate and is associated with a large release of kinetic energy. In contrast, the loss of the halogeno substituents to give type b ions probably occurs via a direct displacement reaction by the sulfur atom of the thioamide group giving rise to Gaussian shaped peaks mass analysed ion kinetic energy spectra.     

Desoxy-nitrozucker 14. Mitteilung 1-C-Nitroglycale. Herstellung und Umsetzung mit einigen Stickstoff-Nucleophilen

1-C-Nitroglycals. Preparation and Reaction with Some Nitrogen Nucleophiles Acetylation of the 1-deoxy-1-nitromannopyranoses 2 and 6 was accompagnied by spontanous β-elimination to give the 1-C-nitroglucals 3 and 7 , respectively, while acetylation of the gluco- and galacto-configurated 1-deoxy-1-nitropyranoses 8 and 14 gave the acetates 9 and 15 , respectively (Scheme 1). The acetylation of the ribo- and arabino-configurated 1-deoxy-1-nitrofuranoses 19 and 21 also occurred without β-elimination to give the acetates 20 and 22 , respectively (Scheme 2). Mild base treatment of the previously described O-acetylnitro-β-D -glucose 4 , the O-acetylnitro-β-D -pyranoses 9 and 15 , and the O-acetylnitro-β-D -furanoses 17 , 20 , and 22 gave the 1-C-nitroglycals 3 , 10 , 16 , 18 and 23 , respectively (Scheme 1 and 2). The previously obtained 1-C-nitroglucal 3 was deacetylated by treatment with MeOH in the presence of KCN or sodium m-nitrophenolate to give the free nitroglucal 5 . Deacetylation of the benzylidene protected 1-C-nitroglucal 10 (MeOH, NaOMe) gave the 4,6-O-benzylidene-1-C-nitroglucal 11 and traces of the 2-O-methyl-1-C-nitromannoses 12 and 13 . The UV, IR, ¹H-NMR and ¹³C-NMR spectra of the 1-C-nitroglycals are discussed. In solution, the 1-C-nitroglycals 1 , 5 , 7 , 10 , 11 , and 16 adopt approximately a ⁴H_5? and 3 a flattened ⁴H₅ conformation. The structure of 5 was established by X-ray analysis. In the solid state, 5 adopts a sofa conformation, which is stabilized by an intramolecular H-bond. The β-addition of NH₃ to the 1-C-nitroglucals 7 and 10 was followed by an O→ N acetyl migration to give exclusively anomeric pairs of the N-acetyl-1-nitromannosamine derivatives 24 / 25 and 26/27 , respectively (Scheme 3). The β-addition of methylamine, octadecylamine, and tryptamine to the 1-C-nitroglucal 11 also stereoelectronically controlled and gave the crystalline N-alkyl-1-nitromannosamines 28 , 29 , and 30 , respectively. The stereoelectronically controlled β-addition of NH₃ to the 1-C-nitrogalactal 16 , followed by acetylation, yielded exclusively the talosamine derivative 31 , while the reversible β-addition of azide ions to 16 gave the anomeric 2-azido-1-nitrogalactoses 32 and 33 . The β-addition of azide ions to the 1-C-nitroglucal 1 led to the 2-azido-1-nitromannose 34 . In the presence of excess formaldehyde, this addition was followed by a Henry reaction. Chromatography of the crude product was accompagnied by solvolytic removal of the NO₂ group to give the 3-azidomannoheptulose 35 in high yields (Scheme 4).     

Chemistry of thienopyridines. XXXIV. Mass spectral fragmentation patterns of some secondary amines and related imines

The mass spectra of some secondary amines and aldimines in the thieno[2,3-b]pyridine ( 3 ) system are presented. α, α-Bis(4-thieno[2,3-b]pyridylamino)toluene ( 1 ) undergoes (a) electron impact-induced dissociation at 80° to give the spectrum of 4-amino- 3 (3b) and (b) thermal dissociation at 200° to give a composite spectrum of 3b and its benzylidene derivative. Spectra of benzylamino and dimethylaminobenzylamino derivatives of 3 are dominated by benzyl-type fragments, while benzylideneimino derivatives show more varied fragmentation.     

Electron impact mass spectrometry of some 6-substituted tetrazolo[1,5-c]pyrimidin-5(6H)-ones

The electron impact mass spectra of 6-methyltetrazolo[1,5-c]pyrimidin-5(6H)-one, its 7- and 8-methyl derivatives, three 8-halo derivatives and two related nucleosides are reported. On the basis of the high-resolution data and detected metastable ions, the fragmentation routes of their molecular ions are proposed. Coexistence of the tautomeric forms of the title compounds of cyclic (tetrazole) or linear (azide) structure can be suggested owing to the fragmentation pathways identified for the bases. Decomposition of the related nucleosides lies in the breaking of nucleoside bonds to produce the appropriate base and sugar fragments.     

Recherches en série azabenzodiazépine. VI—etude en spectrométrie de masse de pyrazolo [3,4-b]diazépines-1,4

The mass spectra of 21 1,4-pyrazolo[3,4-b]diazepines are reported and analysed. Each of the five structures of the diazepine ring present is characterized by a particular group of fragmentations; among them one is common to all the compounds under study: the cleavage of C-5? C-6 and C-7? N-8 bonds leading to pyrazoloimidazoles ions.     

Mass spectrometry of modified nucleic acid bases and nucleosides. 2. Class II mesoionic nucleosides and bases derived from thiazolo[3,2-a]pyrimidine-5,7-diones

The mass spectral characteristics of novel Class II mesoionic heterocyclic bases and nucleosides based on the thiazolo[3,2-a]pyrimidine-5,7-dione system have been examined using low and high resolution mass spectrometry and metastable ion analysis. The mass spectra of these Class II mesoionic nucleosides differ significantly from the spectra of “normal” nucleosides by the absence of fragment ions associated with the base plus portions of the sugar. The difference in fragmentation is rationalized on the basis of exclusive localization of the radical-charge site in the aglycone, a result of the mesoionic structure of these molecules. The fast atom bombardment (FAB) mass spectra of a Class I mesoionic nucleoside, 7-methylguanosine, is compared to the FAB mass spectra of the Class II mesoionic nucleosides.     

Doubly charged ion mass spectra: VI—Amines

Doubly charged ion mass spectra of 22 amines (2–10 carbon atoms) were determined using an Hitachi RMU-7L double focusing mass spectrometer. Molecular ions were not observed in the spectra of aliphatic amines. The most intense product ion peaks in the spectra of lower molecular weight amines resulted from hydrogen elimination from the molecular ion; however, as amine molecular weight increased the largest peaks resulted from both hydrogen and heavy atom elimination from the molecular ion. Dominant ions in the doubly charged ion spectra of lower molecular weight aliphatic amines were from reactions of [C_nH₃N]²⁺ (n:=2, 3, 4) type ions. The spectra of higher molecular weight aliphatic amines spanned a wide mass range. Appearance energies for some of the more prominent ions were measured in the range from 25 to 49 eV. A geometry optimized quantum mechanical self-consistent field molecular orbital treatment was used to compute the energies and structural parameters of prominent ions in the doubly charged ion mass spectra.     

Stereospecific fragmentation processes in cycloalkane/cycloalkene-fused isomers of saturated pyrrolo[2,1-b][1,3]oxazin-6-one derivatives

Electron ionization-induced fragmentations were studied in a set of saturated pyrrolo[2,1-b][1,3]oxazin-6-one derivatives fused to either cycloalkane or cycloalkene rings, including seven pairs of cis/trans and endo/exo annelation isomers. Fragmentation patterns were confirmed by accurate mass measurements and metastable ion spectra. A number of striking differences were observed between the mass spectra of cyclohexene-fused isomers due to highly stereospecific retro-Diels-Alder (RDA) fragmentation of their M^+· ions. The observed 90% stereospecificity is abnormally high in the light of the recent classification (A. Mandelbaum, 1994) of stereospecific RDA fragmentations according to the degree of substitution of the cyclohexene ring being cleaved. In the absence of RDA processes, the differences between the mass spectra of cyclohexane-fused isomers originated from heterocyclic fragmentations. The assumed mechanistic interpretation of the observed differences, e. g., in the formation of [M − C₃H₅O]⁺ ions, was consistent with the condensed-state conformations of these isomers determined previously by NMR and X-ray diffraction studies. Because of rapid RDA decompositions of their rather unstable M^+· ions, the spectra of the diendo/diexo norbornene-fused isomers were virtually identical.     

Reaction of Tertiary 2-Chloroketones with Cyanide Ions: Application to 3-Chloroquinolinediones

3-Chloroquinoline-2,4-diones react with cyanide ions in dimethyl formamide to give 3-cyanoquinoline-2,4-diones in small yields due to the strong hindrance of the substituent at the C-3 atom. Good yields can be achieved if the substituent at this position is the methyl group. In the methanol solution, the reaction proceeds by an addition mechanism to form 2-oxo-1a,2,3,7b-tetrahydrooxireno[2,3-c]quinoline-7b-carbonitriles, from which 4-hydroxy-3-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline-4-carbonitriles are subsequently formed by opening of the epoxide ring with methanol. Some minor products of these reactions have also been isolated. The ¹H, ¹³C and ¹⁵N NMR spectra of the prepared compounds were measured, and all resonances were assigned using appropriate two-dimensional spectra.