Mass spectrometry and pyrolytic decomposition of 2-amino-3′,4′,6-trisubstituted isoflavones

The 2-aminoisoflavones studied exhibited some familiar fragmentation pathways, such as the formation of the retro-Diels–Alder ions. However, substitutions at C(2), C(3′), C(4′) and C(6) induced some specific decompositions of both mass spectrometric and pyrolytic origin. Pyrolytic decompositions reverse to the Mannich reaction occurred with all compounds to variable extents. The three compounds with the (Me)₂NSO₂ substitution at C(6) exhibited another type of pyrolytic reaction, namely the formation of products corresponding to ions of m/z 272, 300 and 314, depending on the type of substitution at C(3′). The occurrence of an interesting ‘ortho effect’, the elimination of the elements of CH₃O from C(3′) and C(4′), was also established.     

Synthesis of 2′-amino-2′-deoxy-5-fluorocytidine

Acetylation of 2′-deoxy-5-fluoro-2′-trifluoroacetamidouridine with acetic anhydride in pyridine, followed by treatment with phosphorus pentasulfide in refluxing dioxane afforded 3′,5′-di-O-acetyl-2′-deoxy-5-fluoro-2′-trifluorothioacetamido-4-thiouridine ( 3 ). Treatment of 3 with methanolic sodium methoxide furnished 2′-deoxy-2′-trifluorothioacetamido-4-thiouridine ( 4 ), whereas its treatment with methanolic ammonia gave 2′-amino-2′-deoxy-5-fluorocytidine ( 5 ). An alternative approach for the preparation of this compound proceeding from 2′-trifluoroacetamidocytidine was unsuccessful, since the use of acetic anhydride in pyridine led to the replacement of the trifluoroacetyl function by an acetyl group, yielding an intermediate unsuitable for obtaining the target compound. The title compound was inactive at 1 × 10^?4 M concentration against HeLa and leukemia L1210 cells in vitro, but inhibited the in vitro growth of E. coli cells at a concentration of 1 × 10^?7 M. It was also found to be a substrate for CR/dCR deaminase partially purified from human liver, with a Km of 128 μM.     

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.     

Mass spectrometry of charge-transfer complexes of 7,7′,8,8′-tetracyanoquinodimethane-π-donor systems

Electron impact (El) ionization and positive and negative liquid secondary ion mass Spectrometry (pLSIMS and nLSIMS) of eight charge-transfer complexes of 7,7′,8,8′-tetracyanoquinodimethane (TCNQ)-aromatic systems and of the individual π-donors and -acceptors was examined. The El spectra exhibited the molecular ions of both the donor and the acceptor of each complex. The molecular ion of the π-donor was observed in pLSIMS using m-nitrobenzyl alcohol (NBA) if its oxidation potential is lower than 1.2 V, but when the oxidation potential is higher than 1.9 V, no molecular ion was detected. On the other hand, nLSIMS exhibited the molecular ion of TCNQ in all cases. Participation of an excited state of NBA in the ionization process is suggested.     

New heterocyclic derivatives of 1′- and 3′-amino-5′,6′,7′,8′-tetrahydro-2′-acetonaphthones

The preparation of 1′-and 3′-amino-5′,6′,7′,8′-tetrahydro-2′-acetonaphthones (IIIa and IIIb) is described, by reduction of the low temperature nitration products of 5′,6′,7′,8′-tetrahydro-2′-acetonaphtone (I). The structures of the nitro isomers (IIa and IIb), and the reduction products, IIIa and IIIb, were elucidated spectroscopically. By known reactions, a series of new heterocyclic compounds prepared from the o-aminoketones, IIIa and IIIb, resulted in two series of new heterocyclic compounds.     

Mass spectrometry of 7,7′,8,8′-tetracyanoquinodimethane and of some of its radical anion salts

We present mass spectrometry experiments on tetracyanoquinodimethane (TCNQ), deuteriated TCNQ and on some TCNQ salts. Apart from the usual nitrile fragmentation, at least two original features appear in the spectra. The first is the formation of TCNQ dimers, as evidenced by their molecular peaks and their fragmentation. The second aspect concerns the spectra of the ammonium salts, which show that hydrogen or alkyl groups add to TCNQ before its decomposition, leading to new fragments (as m/z 141).     

Mass spectrometry of 1,1′-diacetylferrocene and 1,1′-dipropionylferrocene: Evidence for intraannular interaction between alkanoyl substituents

The mass spectra of 1,1′-diacetylferrocene, 1,1′-dipropionyl ferrocene and their deuterium and Fe⁵⁷ isotope labeled analogs are herein reported and discussed. Fragmentation pathways are established and evidence is presented that in the process of fragmentation there is extensive interaction between substituents on the two ferrocene rings. This process apparently has little precedent in the mass spectrometry of ferrocene derivatives. Specifically, the experimental results suggest the simultaneous elimination of two molecules of carbon monoxide, or in another case, of carbon monoxide and ethylene from ions produced in the mass spectrometry of the above compounds.     

Mass spectra of some 2-(4′-butyl-3,′5′-dimethylpyrazol-1′-yl)-6-substituted benzothiazoles

The fragmentation of the title compounds on electron impact has been studied and the major processes interpreted. The base peak invariably appears at [M ? 43]⁺ whose origin from the butyl chain has been traced with the help of metastable ion studies and accurate mass measurements. Loss of methyl cyanide, involving the decomposition of the pyrazole moiety, is observed only from the fragment ions.     

Mass spectral rearrangements of N,N-bis(4′-arylthio-2′-butynyl)anilines and N,N-bis(4′-arylsulfonyl-2′-butynyl)anilines

The title compounds display unusual modes of fragmentation under electron impact. One of the dominant modes is the concerted elimination of the two arylthio and arylsulfonyl moieties followed by further extrusion of the C₆H₄ unit as a cumulene. No elimination of SO₂ is observed from any of the sulfones nor an expulsion of the C₄H₄ fragment. Such behavior contrasts strikingly with that of 1,4-diarylsulfonyl-2-butynes and of the 1,6-diarylsulfonyl-2,4-hexadiynes.     

4′‐Iodo‐2,2′:6′,2′′‐terpyridine

In the nearly planar title compound, C₁₅H₁₀IN₃, the three pyridine rings exhibit transoid conformations about the interannular C—C bonds. Very weak C—H...N and C—H...I interactions link the molecules into ribbons. Significant π–π stacking between molecules from different ribbons completes a three‐dimensional framework of intermolecular interactions. Four different packing motifs are observed among the known structures of simple 4′‐substituted terpyridines.     

2′‐Hydroxy‐4′′‐dimethylaminochalcone

The title compound, 3‐[4‐(di­methyl­amino)­phenyl]‐1‐(2‐hydroxy­phenyl)­prop‐2‐en‐1‐one, C₁₇H₁₇NO₂, is a chalcone derivative substituted by 2′‐hydroxyl and 4′′‐di­methyl­amino groups. The crystal structure indicates that the aniline and hydroxy­phenyl groups are nearly coplanar, with a dihedral angle of 10.32 (16)° between their phenyl rings. The molecular planarity of this substituted chalcone is strongly affected by the 2′‐hydroxyl group.     

Synthesis of 2′-amino-17-cyclopropylmethyl-6,7-dehydro-3,14-dihydroxy-4,5α-epoxy-6,7:4′,5′-thiazolomorphinan from naltrexone

Fusion of an azole moiety at C-6 and C-7 of naltrexone ( 1 ) is illustrated by the synthesis of the title compound 8 . Bromination of 3-O-methylnaltrexone led to the 1,7α-dibromo derivative which reacted with thiourea to attach the 2-aminothiazole ring to C-6 and C-7 of naltrexone. After converting the amino and alcohol groups to trimethylsilyl derivatives, the aromatic bromo group was removed by halo-lithium interchange with butyllithium, followed by hydrolysis with water. In the final step of the synthesis, the methyl ether was cleaved by boron tribromide to generate 8 . An alternate synthesis of 8 commenced with 3-O-acetylnaltrexone ( 9 ). Bromination of 9 in acetic acid in the presence of hydrobromic acid produced a mixture of 3-O-acetyl-7α-bromonaltrexone ( 10 ) and 7α-bromonaltrexone ( 11 ), both, as hydrobromides. Reaction of this mixture with thiourea furnished 8 (62% from 1 ). While ¹H and ¹³C chemical shifts of all compounds are reported, those of 11 hydrobromide and 8 dihydrochloride were established unequivocally.     

4′‐Vinyl‐2,2′:6′,2′′‐ter­pyridine

The title compound, C₁₇H₁₃N₃, is a versatile precursor for polymeric ter­pyridine derivatives and their metal complexes. The mol­ecule has transoid and near‐coplanar pyridine rings. However, the vinyl group is forced out of the plane of the terpyridyl moiety by a close H?H contact.     

4,4,4′,4′,7,7′‐Hexamethyl‐2,2′‐spirobichroman

The title compound, C₂₃H₂₈O₂, was obtained from the reaction of acetone with meta‐cresol. The molecular structure consists of two identical subunits which are nearly perpendicular to each other. The oxygen‐containing rings are not planar and the molecule is chiral. The crystal structure consists of chains of molecules of the same chirality arranged along the [010] axis.     

Synthesis of Some Novel Phenyl Substituted Oxothiazolidin- 1’’,3’’,4’’-thiadiazolo-[3’,4’-b]thiazoline of 3β-Substituted Cholestane

Three title compounds 4a—4c have been synthesized by the cyclodehydration of 1’-benzylidine-4’-(3β-substituted-5α-cholestane-6-yl)thiosemicarbazones 2a—2c with thioglycolic acid followed by the treatment with cold conc. H2SO4 in dioxane. The compounds 2a—2c were prepared by condensation of 3β-substituted-5α-cholestan- 6-one-thiosemicarbazones 1a—1c with benzaldehyde. These thiosemicarbazones 1a—1c were obtained by the reaction of corresponding 3β-substituted-5α-cholestan-6-ones with thiosemicarbazide in the presence of few drops of conc. HCl in methanol. The structures of the products have been established on the basis of their elemental, analytical and spectral data.     

Structural and theoretical characterization of a new twisted 4′‐substituted terpyridine compound: 4′‐(isoquinolin‐4‐yl)‐2,2′:6′,2′′‐terpyridine

4′‐Substituted derivatives of 2,2′:6′,2′′‐terpyridine with N‐containing heteroaromatic substituents, such as pyridyl groups, might be able to coordinate metal centres through the extra N‐donor atom, in addition to the chelating terpyridine N atoms. The incorporation of these peripheral N‐donor sites would also allow for the diversification of the types of noncovalent interactions present, such as hydrogen bonding and π–π stacking. The title compound, C₂₄H₁₆N₄, consists of a 2,2′:6′,2′′‐terpyridine nucleus (tpy), with a pendant isoquinoline group (isq) bound at the central pyridine (py) ring. The tpy nucleus deviates slightly from planarity, with interplanar angles between the lateral and central py rings in the range 2.24 (7)–7.90 (7)°, while the isq group is rotated significantly [by 46.57 (6)°] out of this planar scheme, associated with a short H_tpy…H_isq contact of 2.32 Å. There are no strong noncovalent interactions in the structure, the main ones being of the π–π and C—H…π types, giving rise to columnar arrays along [001], further linked by C—H…N hydrogen bonds into a three‐dimensional supramolecular structure. An Atoms In Molecules (AIM) analysis of the noncovalent interactions provided illuminating results, and while confirming the bonding character for all those interactions unquestionable from a geometrical point of view, it also provided answers for some cases where geometric parameters are not informative, in particular, the short H_tpy…H_isq contact of 2.32 Å to which AIM ascribed an attractive character.     

Mass spectra of some 1-(6′-substituted-4′-methyl-2′-quinolyl)-3-methylpyrazol-5-ols and their 4-substituted analogues

Electron impact induced fragmentation of some 1-(6′-substituted-4′-metbyI-2′-quinolyI)-3-methylpyrazoI-5-ols follows a route where the pyrazole moiety is preferentially cleaved with successive losses of two moieties of 41 u. High-resolution measurements have established that the first loss is due to the ?₂HO moiety, which necessitates an intramolecular hydrogen transfer followed by ring fission. The resultant ion loses CH₃CN in a subsequent step. The origin of many fragment ions was traced with the use of B/E linked-scan spectra.