Heterocyclic Quaternary Salts Research Articles

Brønsted acid-mediated tandem cyclization of triarylphosphines and in situ generated ortho-alkynyl quinone methides: access to heterocyclic quaternary phosphonium salts.

Heterocyclic Quaternary Phosphonium Salts (HQPS) have emerged as promising chemicals for organic synthesis and medicinal chemistry. However, the present synthetic methodology of this type of compound is still limited. Here, we report a deconstructive reorganization strategy based on Brønsted acid-mediated tandem 1,4 addition/intramolecular cyclization of triphenylphosphine derivatives and in situ generated o-AQMs for the first time. This protocol provides a novel approach to heterocyclic quaternary phosphonium salts. The method also features a non-metal catalyst, mild reaction conditions, high efficiency and wide substrate scope. Moreover, a series of obtained heterocyclic phosphonium salts can be converted to isotopically labelled 2-benzofuran compounds directly by simple deuteration reactions.

Systems with annulated thioxo azepinone moiety: an access through heterocyclic carbodithioate ring expansion

New 1-oxo-2-thioxo-1,2,4,5-tetrahydrobenz[d]azepine and 1-oxo-2-thioxo-1,2,4,5-tetrahydroazepino[4,5-b]indole derivatives were conveniently obtained by the novel recyclization reaction of (methylthio)carbonothioylsubstituted heterocyclic quaternary salts with expansion of the dihydropyridine ring.

A general method for the synthesis of heterocyclic dithiocarboxylate betaines: Potential precursors of NHC based on a novel type of functionalization of the methyl group

A more general, non-carbene route to heterocyclic dithiocarboxylate betaines was developed based on a novel type of functionalization of the C-methyl group of heterocyclic quaternary salts under the action of sulfur. These types of betaines are of interest as possible precursors for N-heterocyclic carbenes and metal complex catalysts.

Synthesis and Photophysical Properties of Novel Highly Stable Zero/Bis-Zero Methine Cyanine Dyes Based on N-Bridgehead Heterocycles

Cyanine dyes of zero/bis-zero methine incorporating imid-azo(1,2-a)Pyridine (quinoline) or pyrazino(1,2-a)pyridine (quinoline) with stable C-N bond were synthesized using keto-oxime methylene C-link heterocyclic quaternary salts [1-phenyl-3-methyl-pyrazolino-4-keto-oxime-α-methylene-bis-pyridin-(quinoin)-1(4)-di-ium-iodide(ethiodide) salts and 1-phenyl-3-methyl-pyrazolino- 4-ketooxime-α-methylene-N-2-methyl-bis pyridin (quinoin)-1(4)-di-ium-iodide(ethiodide) salts]. Such heterocyclic precursors and related dyes were identified by elemental and spectral analyses. The absorption spectra properties of such dyes were investigated in 95% Ethanol to attempt and throw some light on the influence of such new heterocyclic nuclei and to compare or evaluate spectral behaviors. The absorption spectra of dyes in different pure solvents were examined in the visible region showing solvatochromism and the colour changes of dyes with solvents having different polarities. This permits a selection of the optimal solvent (fractional solvent) when such dyes are applied as photosensitizers. The spectral behavior of some selected newly synthesized cyanine dyes is observed in mixed solvents of different polarities and progressively increasing quantities of one solvent over the other were studied and showed an increase in the absorbance of CT band with increasing proportion of that solvent. Evidence for hydrogen bond formation between the solute molecules and solvent molecules allows measurement of certain energies such as hydrogen bonding, orientation, and free energies.

Red-Fluorescent Activatable Probes for the Detection of Hydrogen Peroxide in Living Cells.

Many inflammatory processes are associated with an increase in the production of reactive oxygen species (ROS). Chemical probes that specifically detect ROS are potentially useful tools for the early diagnosis of inflammatory diseases as well as cancer. Herein we have developed a library of coumarin hybrids by condensation of various heterocyclic quaternary salts to a 7-hydroxycoumarin scaffold. From our library we identified one benzothiazole-coumarin hybrid as a red-fluorescent compound with emission maxima around 620 nm and a strong fluorogenic response. Furthermore, we proved that this scaffold is suitable for the preparation of activatable probes, such as by modification with a boronate group for selective sensing of hydrogen peroxide (H2O2). In vitro assays confirmed the reactivity and subsequent emission of our probe upon incubation with H2O2 with good selectivity over different ROS and reactive nitrogen species (RNS) as well as minimal toxicity in cells. Finally cell imaging experiments were performed in murine macrophages and validated the utility of the activatable probe for the detection of H2O2 in living cells.

Interaction of Molybdo-Phosphoric and Molybdo-Antimono-Phosphoric Heteropoly Acids with Silica Gels Modified with Aliphatic and Heterocyclic Quaternary Ammonium Salts

The interaction of molybdo-phosphoric and molybdo-antimonophosphoric heteropoly acids with aliphatic (tetradecylammonium nitrate and trinonyloctadecylammonium iodide) and heterocyclic (lucigenine and safranine) quaternary ammonium salts immobilized onto silica has been studied using adsorption and spectroscopic methods. It has been shown that the formation of ionassociates between the quaternary ammonium cations and the heteropoly anions is accompanied by their interaction with surface silica groups which accounts for the tight binding of heteropoly acids to the surface. Such interfacial reactions can successfully be applied to the development of spectroscopic and semi-quantitative visual test techniques for detecting trace amounts of phosphorus and antimony.

Synthesis of a new β-naphthothiazole monomethine cyanine dye for the detection of DNA in aqueous solution

Novel monomethine cyanine dye (MC) derived from beta-naphthothiazole and benzothiazole has been prepared and characterized by (1)H and (13)C NMR, FTIR, ESIMS, elemental analyses, absorption and fluorescence spectroscopy. The dye was conveniently synthesized by the condensation of two sulfate heterocyclic quaternary salts. The interaction between calf thymus DNA (ct-DNA) in tris(hydroxymethyl)aminomethane-HCl (Tris-HCl) aqueous buffer solution and MC has been studied with spectral fluorescence method. The binding constant value has been determined by fluorescence titration of MC with ct-DNA concentrations. The result obtained is consistent with an intercalative binding interaction between MC and ct-DNA. Compared with ethidium bromide (EB), MC showed a huge fluorescence enhancement upon mixing with ct-DNA.

New amino and acetamido monomethine cyanine dyes for the detection of DNA in agarose gels

Some new monomethine cyanine dyes derived from quinoline and benzothiazole have been prepared and characterized by 1H and 13C NMR, FTIR, FABHRMS, and visible spectroscopy. The dyes containing amino and acetamido groups were conveniently synthesized by the condensation of two p-toluenesulfonate heterocyclic quaternary salts and were obtained in the forms of iodide, bromide, and tosylate counteranions. These dyes were compared to ethidium bromide as stains for DNA in electrophoretic gels. The overall results obtained for the sensitivity of these dyes suggest the suitability of acetamido moiety over the amine one and bromide as the counteranion when compared with iodide and tosylate, with a similar capacity of DNA detection in relation to the ethidium bromide stain over the concentration range of 1–3 ng.

The use of N-bridgehead heterocyclic indolizinium ylide in the synthesis of aza-cyanine dyes

The reaction of 3-methyl-8-oxime-1-phenylpyrazolo [4,5- d]indolizinium (bezoindolizinium) ylide iodide with 2(4)-methyl substituted heterocyclic quaternary salts give 8[2(4)]-aza-monomethine cyanine dyes. Meanwhile, the reaction with carbonyl compounds followed by reaction with 2-methyl quinolinium methiodide salts afforded 5(2)-aza-trimethine cyanine dyes. On the other hand, the reaction of 5-formyl-2-methyl-4-phenylpyrazolo[4,5- d]indolizinium (benzoindolizinium) ylide iodide with hydroxylamine hydrochloride followed by reaction with N-methyl heterocyclic quaternary salts afforded the corresponding 5[4(1)]-aza-dimethine cyanine dyes. These new compounds are characterized with elemental analyses, visible absorption, IR, 13C NMR, 1H NMR and mass spectroscopy. The correlations between the structure and spectral properties of these dyes have been studied.

The use of oxonium salts in the synthesis of mono-, β-substituted dimethine and styryl cyanine dyes

Pyrazolopyrylium perchlorate salt derivatives were obtained from the reaction of 5-chloro-4-formyl-1-phenyl pyrazole with phenylpyrazolone, [4(2-propenyl)-1,6-ene-2-cyclohexanone] and cyclohexanone give pyrazolopyrylium perchlorate salt derivatives. Reaction of the latter compounds with 2(4)-methyl substituted heterocyclic quaternary salts gave the pyrazolopyrylium 4[2(4)]-monomethine cyanine dyes. Meanwhile, reaction with amide compounds gives an intermediate compounds which when reacted with 2(4)-methyl substituted heterocyclic quaternary salts gave the pyrazolopyrylium 4[2(4)]-β-substituted dimethine. Reaction of the intermediate compounds with various aromatic aldehydes followed by the reaction with 2-methyl quinolinium ethiodide salt give bis styryl cyanine dyes. Elemental analyses, visible absorption, IR, 1H NMR spectroscopy and mass spectra established the structures of these compounds. The relationship between the structure and properties of these dyes is discussed.

Synthesis and antimicrobial activity of meso-substituted polymethine cyanine dyes

The condensation reaction of equivalent amounts of 2-cyanomethyl benzooxazole or its derivatives with variously substituted aromatic aldehydes gave 2-cyano-styryl benzooxazole or its derivatives. The subsequent reaction of the 2-cyano-styryl benzooxazoles with 2(4)-methyl substituted heterocyclic quaternary salts afforded meso-substituted styryl-2(4)-polymethine cyanines. The condensation reaction of 2-cyanomethyl benzooxazole or its derivatives with α-nitroso-β-naphthol followed by reaction with 2(4)-methyl substituted heterocyclic quaternary salts gave meso-substituted aza-2(4)-polymethine cyanines. The reaction of 2-cyanomethyl benzooxazole or its derivatives with N-methyl heterocyclic quaternary salts followed by the reaction with 2-methylquinolinium methiodide afforded the corresponding meso-substituted trimethine cyanine dyes. Elemental analyses, visible absorption, IR, 1H NMR spectroscopy, and mass spectra established the structures of these compounds. The relationship between the structure and properties of these dyes has been studied and the solvatochromic behavior of some selected cyanine dyes in organic solvents is discussed. Finally, the antimicrobial activity of selected novel dyes was investigated in vitro using a wide spectrum of microbial strains.

Synthesis and antimicrobial activity of certain novel monomethine cyanine dyes

A series of novel monomethine cyanine dyes were synthesized by using 3-methyl-5-substituted-1-phenyl-pyrano[2,3-c]pyrazole derivatives 2a– c. Reaction of equimolar ratios of 2a– c with 2(4)-methyl heterocyclic quaternary salts afforded the corresponding monomethine cyanines 3a– c. Reaction of compound 5 with 2(4)-methyl heterocyclic quaternary salts gives monomethine 6a– c. Condensation reaction of equimolar ratios of compounds 7 and 9a, b with 2(4)-methyl heterocyclic quaternary salts afforded the corresponding monomethine cyanines 8a– c and 10a, b respectively. The new synthesized monomethine cyanine dyes were identified by elemental analyses, IR, 1H-NMR and Ms spectral data. The electronic absorption spectra in ethanolic solution of novel monomethine cyanine dyes were measured and the antimicrobial activity of some selected monomethine cyanine dyes was discussed.

Spiro-Azoles Thiazolidinone in the Synthesis of Polymethine Cyanine Dyes

A series of some spiro azoles (pyrazolone, oxazolone, and/or imidazolone) inconjucton with heterocyclic thiazolidinone derivatives were prepared as starting materials in the synthesis of polymethine cyanine dyes. Reaction of spiro 2-formyl (oxime) azoles thiazolidinone derivatives with equi- and/or molar ratios of 2(4)-methyl substituted heterocyclic quaternary salts afforded the corresponding compound pentamethine, aza-mero cyanine, and azapentamethine cyanine dyes respectively. Elemental analyses, IR, 1 H-NMR, and mass-spectra identified the new spiro heterocyclic compounds and polymethine cyanine dyes. The visible absorption spectra of all new polymethine cyanine dyes were investigated.

Utilization of charge and mass labeling for the structural identification of heterocyclic quaternary salts by mass spectrometry

Heterocyclic compounds of general formula C ++2Br − were studied by tandem mass spectrometry. Fragmentations taking place from the [CH] + and [CBr] + ions allowed identification of their structures. The two fundamental data of mass spectrometry, mass and charge, have been employed for characterization purposes.

The synthesis of some bridgehead heterocyclic monomethine cyanine dyes

α-Chloroacteic acid and phenacyl bromide were used as reagents reacting with 8-hydroxyquinoline to form bridgehead heterocycles. Reaction of these heterocycles with equi-or bis-molar ratios of 2-(or 4-)methyl substituted heterocyclic quaternary salts afforded a series of monomethine and bismonomethine cyanine dyes. The electronic spectra of the monomethine cyanine dyes in various solvents are discussed. ©

Novel heterocyclic dyes as DNA markers. Part I. Synthesis and characterization

A range of new cyanine dyes has been prepared and characterised. These dyes are more conveniently synthesised by the reaction of two heterocyclic quaternary salts. The dyes contain a purine heterocycle coupled to an aro-(thia-, selena-, oxa-, imida)zole and are in the form of iodide or p-toluenesulphonate salts. Characterisation were done by FABMS and NMR spectroscopy. These dyes can be used as fluorescent dyes for DNA marking in the diagnosis of malaria parasites.

Herstellung, Struktur und Eigenschaften neuartiger kettensubstituierter und chiraler Trimethincyanin‐Farbstoffe mit Indolin‐Endgruppen1)

Synthesis, Structure, and Properties of Novel Chain-Substituted and Chiral Trimethine Cyanine Dyes with Indoline End Groups Synthesis and spectroscopic properties of the trimethine cyanine dyes 3, 8a, b, and 13a, b as well as 14a-c with new substitution patterns are described. Constitutions and configurations of 3, 8a, b and 14c have been determined by X-ray analyses (Figures 1, 2, and 6). Dye 3 exists in the previously unknown di-cis (E, E, Z, Z) configuration along the methine chain. Attempts to prepare 3 in a base-catalysed reaction unexpectedly led to the rearranged trimethine cyanine dyes 8a, b with a centre of chirality in one of the indoline end groups. Using this Wagner-Meerwein rearrangement after resolution, the chiral heterocyclic quaternary salts (S)-12a- c have been prepared, from which the optically active trimethine cyanine dyes (S,S)-14a-c have been obtained for the first time. The UV/VIS spectra of 3, 8a and 13a (Figure 7) as well as the CD spectra of 12a and 14a (Figures 3 and 4) are compared and discussed.

Electronic absorption spectra of some new heterocyclic azomethines derived from nitroso and active methyl compounds

The electronic spectra of some new heterocyclic azomethines derived from nitroso compounds and active methyl heterocyclic quaternary salts were studied. The main visible band appearing in the spectra of dialkylamino derivatives is assigned to an intramolecular charge transfer (CT) transition. On the other hand the visible spectra of o-hydroxy compounds are interpreted on the principle of the possible existence of such compounds in a enol ⇌ keto tautomeric equilibrium. In addition the p K a values of these compounds were determined and discussed in terms of molecular structure.

Reactions of some heterocyclic quaternary salts with trifluoroacetic anhydride

Treatment of the methiodides of 4a-methyl-1,2,3,4-tetrahydro-4aH-carbazole, 2-methyl-3H-indole-3-spirocyclopentane, 2-methylbenzothiazole, and 2-methylquinoline with trifluoroacetic anhydride afforded trifluoromethyl ketones. Some reactions of these enaminones with nitrogen-containing nucleophiles are described, attack taking place at the carbon–carbon and the carbon–oxygen double bonds.

Isotopic exchange in heterocyclic quaternary salts. II. (1) Hydrogen‐deuterium exchange ln active c‐methyl groups

AbstractThe non‐catalysed H‐D exchange in heterocyclic quaternary ammonium salts (1–3) was studied by 1H‐nmr. Exchange occurs only at the C‐CH3 group, at a rate decreasing in the order X = C(CH3)2, Se, CH=CH, S, NCH3. In substituted benzothiazolium salts the exchange rates decrease in the series Y = NO2, Cl, H, OCH3. Chemical shifts (δ) of C‐CH3 and N‐CH3 groups decrease in the same sequence. Both exchange rate constants and chemical shifts can be related ta Hammett σp‐ values of the Y substituents. The mechanism p of the exchange reaction is briefly discussed.