Effect of substituents and protonation on the mechanism of 1,3-dipolar retro-cycloaddition reaction of pyrrolidino[60]- and [70]fullerenes

The mass spectra of new substituted pyrrolidino[60]- and [70]fullerenes have been obtained using electrospray ionization conditions in the positive and negative mode of detection with two different mass spectrometers, a quadrupole ion trap and a Fourier transform ion cyclotron resonance. Radical anions M(●-) and deprotonated molecules [M-H](-) are formed under negative electrospray ionization mass spectrometry conditions, and the collision-induced dissociations of both ionic species have been studied. Either negative odd-electron ions or negative even-electron ions undergo a retro-cycloaddition process forming the corresponding fullerene product ions C(60)(●-) and C(70)(●-). The generation of fullerene radical anions from deprotonated molecules is a new exception of the "even-electron rule." In contrast, the protonated molecules [M + H](+) obtained from the positive mode of detection do not undergo this cycloreversion reaction, and the MS(n) experiment reveals a variety of eliminations of neutral molecules involving different hydrogen shifts and multiple bond cleavages that lead eventually to substituted methanofullerene fragment ions. The observed fragmentations can be correlated with the electronic character of the substituents attached to the heterocyclic moiety. The results obtained from the thermal reactions of these compounds, carried out under different pH conditions, correlate well with those obtained in gas phase. The different behaviors between protonated and unprotonated molecules and ions can be explained assuming that the retro-cycloaddition reaction takes place only when the nitrogen atom of the pyrrolidine ring (the basic center of the molecule) is unprotonated both in gas and condensed phase. The protonation of the NH group inhibits the cycloreversion process, and therefore different fragmentations take place. The detailed mechanisms of the formation and evolution of the intermediate fragments are described.     

Basicities of some 9-substituted acridine-4-carboxamides: A density functional theory (DFT) calculation

Acid-base properties of drugs are important in understanding the behaviour of these compounds under physiological condition. In order to understand such behaviour the proton affinities of acri-dine 4-carboxamides with substitution (R) at the 9-position are theoretically studied, and considered for the basic sites of both the heterocyclic ring as well as side chain nitrogens. In 9-amino acridine 4-carbox-amide, the -NH₂ group is observed to be an additional basic site. The heterocyclic nitrogen of substituted carboxamides (R =-NH₂, -O-methyl, -O-ethyl, and -O-phenyl) is more basic than the side chain nitrogen, however, side chain nitrogen corresponds to more basic site for some carboxamides (R = -OH and-Cl) and the -NH₂ group represents the least basic site of 9-amino acridine 4-carboxamide. In addition to presenting the basicities of these drugs an indication of another hydrogen-bond between heterocyclic ring N and carboxamide chain O is observed. The difference of basicities with substituents at 9-position are very narrow and carboxamides with substituents at 9-position are found to be suitable for studying intramolecular H-bonds between the heterocyclic N and carboxamide O. The resultant stabilization of a configuration due to such H-bonding is determined     

Formation of hexagonal columnar phases by heterocyclic pyrimidine derivatives

The synthesis, characterization, and mesomorphic properties of a new type of heteronuclear compounds derived from pyrimidine as core group are reported. These compounds were prepared by condensation reactions of appropriate acetophenones and benzonitriles in the presence of trifluoromethanesulphonic anhydride. They were characterized by ¹H and ¹³C NMR spectroscopy and elemental analysis, and their phase transitions characterized and studied by thermal analysis and polarizating microscopy. These compounds exhibit hexagonal columnar (Col_h) phases, as expected for disk-like molecules; the formation of columnar phases was found to be dependent on the numbers of alkoxy side chains attached. For those compounds having the same numbers of flexible side chains attached, the one with a preferred unsymmetric structure exhibited better mesomorphic properties. The observed improved mesomorphic behaviour of these compounds over other similar all-carbon heterocyclic compounds is attributed to the greater polarization of nitrogen atoms in the core ring.     

NMR spectroscopic investigation of multi-walled carbon nanotubes modified by amino groups

The results of the functionalization of multi-walled carbon nanotube surface by amines containing different substituents at the nitrogen atom, namely, primary n-hexylamine, secondary izadrine, and tertiary N-benzylmorpholine and dithiline, are presented. It was shown by NMR spectroscopy, thermal analysis, mass spectrometry, X-ray photoelectron spectroscopy, and elemental analysis that the interaction of primary and secondary amines with modified nanotubes results in the formation of a covalent bond with the nitrogen atom of amines, while the reactions with tertiary amines afford quaternary ammonium salts; diamine is attached covalently through both amine groups.     

Formation of diaryl sulfides and sulfoxides: Synthesis,characterization and structure activity correlation studies

Abstract

The synthesis of a series of stable diarylsulfides and sulfoxides is reported. All the newly synthesized compounds were characterized by ¹H, ¹³C NMR and mass spectroscopic techniques. A detailed mechanistic study indicates that the formation of sulfoxides follows the oxidation. In addition to synthesis, characterization and mechanistic studies, the glutathione peroxidase(GPx) mimetic activity of the newly synthesized compounds is described. It is observed that the diaryl sulfides having a heterocyclic ring attached to the nitrogen atom facilitates the oxidation of the sulfur center to form the corresponding sulfoxides. The substituents attached to the nitrogen atom play an important role in the catalytic activity of the substituted diaryl sulfides. The obtained data supports for the higher antioxidant activity of diaryl sulfides than that of the corresponding sulfoxides.     

The electron transfer reactions of cyano substituted pyridines and quinolines with thermally generated diphenyl ketyl

Electron transfer reactions of cyano substituted pyridines and quinolines with thermally generated diphenyl ketyl are reported. When E¹/₂(-) for the heterocycle is less negative than -2V, electron transfer occurs from the ketyl to the heterocyclic base. In some cases the products obtained from the thermal reaction are the same as those obtained from the photochemical reaction with benzophenone and alcohols. In other cases different products are formed. Two bases, 2-pyridinecarbonitrile and 2,4-pyridinedicarbonitrile, undergo regiospecific reactions in which the course of the reaction is determined by the acidity of the medium. A mechanism in which the heterocyclic nitrogen is involved in the substitution process at the 2 position is proposed.     

On the thermal stability of [60]fullerene cycloadducts: retro-cycloaddition reaction of 2-pyrazolino[4,5:1,2][60]fullerenes

2-Pyrazolino[4,5:1,2][60]fullerenes undergo a thermally induced retro-cycloaddition process whose efficiency is influenced by the nature of the C-substituent. C-Aryl-N-Aryl-2-pyrazolino[60]fullerenes (2a-d) poorly undergo a thermal retro-cycloaddition reaction even in the presence of a strong dipolarophile or a metal Lewis acid which, in contrast to other fullerene derivatives, shows their remarkable thermal stability. C-Alkyl-N-Aryl-2-pyrazolino[60]fullerenes (2e-f) show a different behavior, being more vulnerable to the presence of copper triflate and leading to the retro-cycloaddition product (pristine C60) in good yield.     

Highly efficient retro-cycloaddition reaction of isoxazolino[4,5:1,2][60]- and -[70]fullerenes

Isoxazolino[4,5:1,2][60]- and -[70]fullerenes undergo an efficient retro-cycloaddition reaction to pristine fullerene by thermal treatment in the presence of an excess of a dienophile and Cu(II) catalysis, which can be selectively used in the presence of malonate or pyrrolidine cycloadducts. Trapping experiments using N-phenylmaleimide as dipolarophile have shown that the reaction mechanism occurs by thermal removal of the nitrile oxide 1,3-dipole, in a process which is favored by the presence of Cu(II) as the catalyst. The ESI-MS study supports the observed retro-cycloaddition process for both C60 and C70 derivatives. In contrast to previous electrochemical retro-cycloaddition processes observed in fulleropyrrolidines, isoxazolinofullerenes were stable under oxidative conditions.     

Mass spectra of 1,2,4-triazoles—II: Alkyl 1,2,4-triazoles

The mass spectra of monomethyl 1,2,4-triazoles contain fragment ions produced by specific cleavage of the heterocyclic ring. A major fragmentation from many molecular ions involves the elimination of HCN, but loss of N₂ is either very small or completely absent. No N or H scrambling occurs within the triazole ring system, as evidenced by labelling studies. The loss of a hydrogen atom from the molecular ions of 3-alkyl-1,2,4-triazoles (alkyl ? C₂H₅) originates from hydrogens attached to the β carbon and nitrogen atoms.     

Fragmentation of substituted 4-hydroxy-2-quinolones under the influence of electron impact

The general principles of the mass-spectral disintegration of 4-hydroxy-2-quinoline derivatives containing various substituents attached to the nitrogen in the 3 position were established. It was found that the disintegration of 4-hydroxy-2-quinolone and its N-substituted derivatives proceeds primarily through cleavage of the heterocyclic ring, while the principal pathways of the disintegration of 3-acyl derivatives are associated with fragmentation of the acyl group.     

Temperature dependence of the nitrogen-14 nuclear quadrupole resonance frequencies in selected triazine compounds

Symmetric-1,3,5 triazine compounds are heterocyclic ring molecules containing three nitrogen atoms at the 1,3,5 sites. Because of their inherent high symmetry and the existence of a large number of compounds with different chemical groups attached to the ring, this class of compounds is ideally suited to NQR studies. We are reporting measurements of T^★₂ and the temperature dependence of the frequencies for a number of the nitrogen-14 NQR lines in trichloromelamine, cyanuric acid, trichloroisocyanuric acid, cyanuric chloride, and melamine. The results of these measurements yielded T^★₂'s for cyanuric chloride almost an order of magnitude larger than for the other compounds. The variations of the frequencies with temperature appear to be consistent with the Bayer—Kushida model.     

Formation of hexagonal columnar phases by heterocyclic pyrimidine derivatives

The synthesis, characterization, and mesomorphic properties of a new type of heteronuclear compounds derived from pyrimidine as core group are reported. These compounds were prepared by condensation reactions of appropriate acetophenones and benzonitriles in the presence of trifluoromethanesulphonic anhydride. They were characterized by 1 H and 13 C NMR spectroscopy and elemental analysis, and their phase transitions characterized and studied by thermal analysis and polarizating microscopy. These compounds exhibit hexagonal columnar (Col h ) phases, as expected for disk-like molecules; the formation of columnar phases was found to be dependent on the numbers of alkoxy side chains attached. For those compounds having the same numbers of flexible side chains attached, the one with a preferred unsymmetric structure exhibited better mesomorphic properties. The observed improved mesomorphic behaviour of these compounds over other similar all-carbon heterocyclic compounds is attributed to the greater polarization of nitrogen atoms in the core ring.     

Mass spectrometry of heterocyclic compounds. VI—retro-1,3-dipolar cycloaddition and competitive fragmentation reaction of 2,5-diaryl-1,3,4-dioxazoles

The process of retro-1,3-dipolar cycloaddition of 2,5-diaryl-1,3,4-dioxazoles induced by electron-impact is discussed. For this purpose, 2-phenyl-5-p-chlorophenyl-1,3,4-dioxazole was prepared, labelled with ¹⁸O in position 1; the spectrum of this compound showed clear evidence of retro-cycloaddition, the dipole fragment retaining the positive charge. This labelled compound also provides a reliable interpretation of other cleavage modes of the heterocyclic ring. The elemental compositions of the ions considered were determined by exact mass measurements and the metastable transitions were detected through the defocusing technique of the electrostatic sector.     

Synthesis of polycyclic benzofused nitrogen heterocycles via a tandem ynamide benzannulation/ring-closing metathesis strategy. Application in a formal total synthesis of (+)-FR900482

A two-stage "tandem strategy" for the synthesis of benzofused nitrogen heterocycles is described that is particularly useful for the construction of systems with a high level of substitution on the benzenoid ring. The first stage in the strategy involves a benzannulation based on the reaction of cyclobutenones with ynamides. This cascade process proceeds via a sequence of four pericyclic reactions and furnishes a multiply substituted aniline derivative which can bear a variety of functionalized substituents at the position ortho to the nitrogen. In the second stage of the tandem strategy, ring-closing metathesis generates the nitrogen heterocyclic ring. This two-step sequence provides efficient access to highly substituted dihydroquinolines, benzazepines, benzazocines, and related benzofused nitrogen heterocyclic systems. The application of this chemistry in a concise formal total synthesis of the anticancer agents (+)-FR900482 and (+)-FR66979 is described.     

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.     

Phenalenones. IV. Heterocycles from 3-hydroxyphenalenone (I)

3-Hydroxyphenalenone reacts with o-disubstituted benzenes (substituents: NH₂, OH, CH₂OH and SH), aliphatic and aromatic aldehydes to give the various heterocyclic compounds which are fused with phenalene ring. These reactions resemble those of 1,3-cyclohexanediones in many respects.     

Polarography of heterocyclic compounds

The literature data on the principles of the electrochemical reduction of heteroethylene and heteroparaffin compounds (pyrazoline, diazepine, diaziridine, pyran, pyridazone, aziridine, oxaziridine, and other derivatives), cyclic anhydrides, imides, and hydrazides of acids on a dropping mercury electrode are correlated. In addition, the effect of substituents attached to the heterocyclic ring on the polarographic behavior of heterocycles is analyzed.     

Modification of 1-substituents in the 2-azabicyclo[2.1.1]hexane ring system; approaches to potential nicotinic acetylcholine receptor ligands from 2,4-methanoproline derivatives

Successful nucleophilic substitution at a methylene attached to the bridgehead (1-) position of the 2-azabicyclo[2.1.1]hexane ring system opens the way to construction of novel derivatives having a wider range of functional groups attached to the 1-position via a methylene "spacer" (including the beta-amino acid homologue of 2,4-methanoproline) and provides access to epibatidine analogues containing heterocyclic substituents and also to further homologation at the 1-position. Displacements with loss of a nucleofuge (e.g., loss of mesylate anion from the 1-mesyloxymethyl derivative) require thermal activation but proceed without the rearrangement initially anticipated in such a strained bicyclic ring system. A novel tricyclic carbamate intermediate 17 has been isolated; nucleophilic attack on 17 leads directly to the isolation of N-deprotected substitution products (with concomitant decarboxylation).     

Facile Access to Substituted 1,4-Diaza-2,3-Diborinines

Several bis(dimethylamino)-substituted 1,4-diaza-2,3-diborinines (DADBs) were synthesized with variable substituents at the backbone nitrogen atoms. By reaction with HCl or BX₃ (X=Br, I), these species were successfully converted into their synthetically more useful halide congeners. The high versatility of the generated B−X bonds in further functionalization reactions at the boron centers was demonstrated by means of salt elimination (MeLi) and commutation (NMe₂ DADBs) reactions, thus making the DADB system a general structural motif in diborane(4) chemistry. A total of 18 DADB derivatives were characterized in the solid state by X-ray diffraction, revealing a strong dependence of the heterocyclic bonding parameters from the exocyclic substitution pattern at boron. According to our experiments towards the realization of a Dipp-substituted, sterically encumbered DADB, the mechanism of DADB formation proceeds via a transient four-membered azadiboretidine intermediate that subsequently undergoes ring expansion to afford the six-membered DADB heterocycle.     

New flexible synthesis of pyrazoles with different,functionalized substituents at C3 and C5

Syntheses of pyrazoles featuring a functionalized side chain attached to carbon 3 and varying alkyl and aryl substituents attached to carbon 5 are presented. Installation of R = methyl, isopropyl, tert-butyl, adamantyl, or phenyl groups at C5 is reported here, starting by coupling protected alkynols with acid chlorides RCOCl, forming alkynyl ketones, which are reacted with hydrazine to form the pyrazole nucleus. Alcohol deprotection and conversion to a chloride gave 5-substituted 3-(chloromethyl)- or 3-(2-chloroethyl)pyrazoles. This sequence can be done within 2 d on a 30 g scale in excellent overall yield. Through nucleophilic substitution reactions, the chlorides are useful precursors to other polyfunctional pyrazoles. In the work here, derivatives with side chains LCH(2)- and LCH(2)CH(2)- at C3 (L = thioether or phosphine) were made as ligands. The significance of the ligands made here is that by placing a ligating side chain on a ring carbon (C3), rather than on a ring nitrogen, the ring nitrogen not bound to the metal and its attached proton will be available for hydrogen bonding, depending on the steric environment created by R at C5.