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13 pages, 5145 KiB

Open AccessArticle

Development of Triazoles and Triazolium Salts Based on AZT and Their Anti-Viral Activity against HIV-1

by Daniel Machado de Alencar, Juliana Gonçalves, Andreia Vieira, Sofia A. Cerqueira, Cruz Sebastião, Maria Inês P. S. Leitão, Giulia Francescato, Paola Antenori, Helena Soares and Ana Petronilho

Molecules 2021, 26(21), 6720; https://doi.org/10.3390/molecules26216720 - 6 Nov 2021

Cited by 9 | Viewed by 2796

Abstract

We report herein a set of 3′-azido-3′-deoxythymidine (AZT) derivatives based on triazoles and triazolium salts for HIV-1 infection. The compounds were synthesized via click chemistry with Cu(I) and Ru(II) catalysts. Triazolium salts were synthesized by reaction with methyl iodide or methyl triflate in [...] Read more.

We report herein a set of 3′-azido-3′-deoxythymidine (AZT) derivatives based on triazoles and triazolium salts for HIV-1 infection. The compounds were synthesized via click chemistry with Cu(I) and Ru(II) catalysts. Triazolium salts were synthesized by reaction with methyl iodide or methyl triflate in good yields. The antiviral activity of the compounds was tested using two methodologies: In method one the activity was measured on infected cells; in method two a pre-exposure prophylaxis experimental model was employed. For method one the activity of the compounds was moderate, and in general the triazolium salts showed a decreased activity in relation to their triazole precursors. With method two the antiviral activity was higher. All compounds were able to decrease the infection, with two compounds able to clear almost all the infection, while a lower antiviral activity was noted for the triazolium salts. These results suggest that these drugs could play an important role in the development of pre-exposure prophylaxis therapies. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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15 pages, 4138 KiB

Open AccessArticle

A Novel Family of [1,4]Thiazino[2,3,4-ij]quinolin-4-ium Derivatives: Regioselective Synthesis Based on Unsaturated Heteroatom and Heterocyclic Compounds and Antibacterial Activity

by Vladimir A. Potapov, Roman S. Ishigeev, Lyudmila A. Belovezhets and Svetlana V. Amosova

Molecules 2021, 26(18), 5579; https://doi.org/10.3390/molecules26185579 - 14 Sep 2021

Cited by 5 | Viewed by 2205

Abstract

A novel family of [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives was synthesized by annulation reactions of 8-quinolinesulfenyl chloride with unsaturated heteroatom and heterocyclic compounds. It was found that the reactions with 4-pentenoic and 5-hexenoic acids, allyl chloride and bromide, allyl cyanate and vinyl heterocyclic compounds [...] Read more.

A novel family of [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives was synthesized by annulation reactions of 8-quinolinesulfenyl chloride with unsaturated heteroatom and heterocyclic compounds. It was found that the reactions with 4-pentenoic and 5-hexenoic acids, allyl chloride and bromide, allyl cyanate and vinyl heterocyclic compounds (N-vinyl pyrrolidin-2-one and 1-vinylimidazole) proceeded in a regioselective mode but with the opposite regiochemistry. The reactions with vinyl heterocyclic compounds included electrophilic addition of the sulfur atom of 8-quinolinesulfenyl chloride to the β-carbon atom of the vinyl group. In the case of other substrates, the annulation proceeded with the attachment of the sulfur atom to the α-carbon atom of the vinyl group. The antibacterial activity of novel water-soluble compounds against Enterococcus durans, Bacillus subtilis and Escherichia coli was evaluated. Compounds with high antibacterial activity were found. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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17 pages, 1920 KiB

Open AccessArticle

The Highly Regioselective Synthesis of Novel Imidazolidin-2-Ones via the Intramolecular Cyclization/Electrophilic Substitution of Urea Derivatives and the Evaluation of Their Anticancer Activity

by Almir S. Gazizov, Andrey V. Smolobochkin, Elizaveta A. Kuznetsova, Dinara S. Abdullaeva, Alexander R. Burilov, Michail A. Pudovik, Alexandra D. Voloshina, Victor V. Syakaev, Anna P. Lyubina, Syumbelya K. Amerhanova and Julia K. Voronina

Molecules 2021, 26(15), 4432; https://doi.org/10.3390/molecules26154432 - 22 Jul 2021

Cited by 12 | Viewed by 3120

Abstract

A series of novel 4-(het)arylimidazoldin-2-ones were obtained by the acid-catalyzed reaction of (2,2-diethoxyethyl)ureas with aromatic and heterocyclic C-nucleophiles. The proposed approach to substituted imidazolidinones benefits from excellent regioselectivity, readily available starting materials and a simple procedure. The regioselectivity of the reaction was [...] Read more.

A series of novel 4-(het)arylimidazoldin-2-ones were obtained by the acid-catalyzed reaction of (2,2-diethoxyethyl)ureas with aromatic and heterocyclic C-nucleophiles. The proposed approach to substituted imidazolidinones benefits from excellent regioselectivity, readily available starting materials and a simple procedure. The regioselectivity of the reaction was rationalized by quantum chemistry calculations and control experiments. The anti-cancer activity of the obtained compounds was tested in vitro. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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16 pages, 2789 KiB

Open AccessArticle

Heterocyclic Schiff Bases of 3-Aminobenzanthrone and Their Reduced Analogues: Synthesis, Properties and Spectroscopy

by Natalja Orlova, Irena Nikolajeva, Aleksandrs Pučkins, Sergey Belyakov and Elena Kirilova

Molecules 2021, 26(9), 2570; https://doi.org/10.3390/molecules26092570 - 28 Apr 2021

Cited by 20 | Viewed by 3357

Abstract

New substituted azomethines of benzanthrone with heterocyclic substituents were synthesized by condensation reaction of 3-aminobenzo[de]anthracen-7-one with appropriate aromatic aldehydes. The resulting imines were reduced with sodium borohydride to the corresponding amines, the luminescence of which is more pronounced in comparison with the initial [...] Read more.

New substituted azomethines of benzanthrone with heterocyclic substituents were synthesized by condensation reaction of 3-aminobenzo[de]anthracen-7-one with appropriate aromatic aldehydes. The resulting imines were reduced with sodium borohydride to the corresponding amines, the luminescence of which is more pronounced in comparison with the initial azomethines. The novel benzanthrone derivatives were characterized by NMR, IR, MS, UV/Vis, and fluorescence spectroscopy. The structure of three dyes was studied by the X-ray single crystal structure analysis. The solvent effect on photophysical behaviors of synthesized imines and amines was investigated. The obtained compounds absorb at 420–525 nm, have relatively large Stokes shifts (up to 150 nm in ethanol), and emit at 500–660 nm. The results testify that emission of the studied compounds is sensitive to the solvent polarity, exhibiting negative fluorosolvatochromism for the synthesized azomethines and positive fluorosolvatochromism for the obtained amines. The results obtained indicate that the synthesized compounds are promising as luminescent dyes. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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19 pages, 5569 KiB

Open AccessArticle

Direct Amination of Nitroquinoline Derivatives via Nucleophilic Displacement of Aromatic Hydrogen

by Jakub Wantulok, Daniel Swoboda, Jacek E. Nycz, Maria Książek, Joachim Kusz, Jan Grzegorz Małecki and Vladimír Kubíček

Molecules 2021, 26(7), 1857; https://doi.org/10.3390/molecules26071857 - 25 Mar 2021

Cited by 4 | Viewed by 3632

Abstract

The vicarious nucleophilic substitution of hydrogen (VNS) reaction in electron-deficient nitroquinolines was studied. Properties of all new products have been characterized by several techniques: MS, HRMS, FTIR, GC-MS, electronic absorption spectroscopy, and multinuclear NMR. The structures of 4-chloro-8-nitroquinoline, 8-(tert-butyl)-2-methyl-5-nitroquinoline, 9-(8-nitroquinolin-7-yl)-9H [...] Read more.

The vicarious nucleophilic substitution of hydrogen (VNS) reaction in electron-deficient nitroquinolines was studied. Properties of all new products have been characterized by several techniques: MS, HRMS, FTIR, GC-MS, electronic absorption spectroscopy, and multinuclear NMR. The structures of 4-chloro-8-nitroquinoline, 8-(tert-butyl)-2-methyl-5-nitroquinoline, 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one were determined by single-crystal X-ray diffraction measurements. The 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one illustrate the nitro/nitroso conversion within VNS reaction. Additionally, 9-(8-isopropyl-2-((8-isopropyl-2-methyl-5-nitroquinolin-6-yl)methyl)-5-nitrosoquinolin-6-yl)-9H-carbazole is presented as a double VNS product. It is postulated that the potassium counterion interacts with the oxygen on the nitro group, which could influence nucleophile attack in that way. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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16 pages, 2836 KiB

Open AccessArticle

Pyrrole–Aminopyrimidine Ensembles: Cycloaddition of Guanidine to Acylethynylpyrroles

by Olga V. Petrova, Arsalan B. Budaev, Elena F. Sagitova, Igor A. Ushakov, Lyubov N. Sobenina, Andrey V. Ivanov and Boris A. Trofimov

Molecules 2021, 26(6), 1692; https://doi.org/10.3390/molecules26061692 - 17 Mar 2021

Cited by 8 | Viewed by 3107

Abstract

An efficient method for the synthesis of pharmaceutically prospective pyrrole–aminopyrimidine ensembles (in up to 91% yield) by the cyclocondensation of easily available acylethynylpyrroles with guanidine nitrate has been developed. The reaction proceeds under heating (110–115 °C, 4 h) in the KOH/DMSO system. In [...] Read more.

An efficient method for the synthesis of pharmaceutically prospective pyrrole–aminopyrimidine ensembles (in up to 91% yield) by the cyclocondensation of easily available acylethynylpyrroles with guanidine nitrate has been developed. The reaction proceeds under heating (110–115 °C, 4 h) in the KOH/DMSO system. In the case of 2-benzoylethynylpyrrole, the unexpected addition of the formed pyrrole–aminopyrimidine as N- (NH moiety of the pyrrole ring) and C- (CH of aminopyrimidine) nucleophiles to the triple bond is observed. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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14 pages, 2152 KiB

Open AccessArticle

Mechanochemical Aza-Vinylogous Povarov Reactions for the Synthesis of Highly Functionalized 1,2,3,4-Tetrahydroquinolines and 1,2,3,4-Tetrahydro-1,5-Naphthyridines

by José Clerigué, M. Teresa Ramos and J. Carlos Menéndez

Molecules 2021, 26(5), 1330; https://doi.org/10.3390/molecules26051330 - 2 Mar 2021

Cited by 7 | Viewed by 2768

Abstract

The aza-vinylogous Povarov reaction between aromatic amines, α-ketoaldehydes or α-formylesters and α,β-unsaturated dimethylhydrazones was carried out in a sequential three-component fashion under mechanochemical conditions. Following extensive optimization work, the reaction was performed on a vibratory ball mill operating at 20 Hz and using [...] Read more.

The aza-vinylogous Povarov reaction between aromatic amines, α-ketoaldehydes or α-formylesters and α,β-unsaturated dimethylhydrazones was carried out in a sequential three-component fashion under mechanochemical conditions. Following extensive optimization work, the reaction was performed on a vibratory ball mill operating at 20 Hz and using zirconium oxide balls and milling jar, and afforded 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydro- 1,5-naphthyridines functionalized at C-2, C-4 and also at C-6, in the latter case. This protocol generally afforded the target compounds in good to excellent yields and diastereoselectivities. A comparison of representative examples with the results obtained under conventional conditions revealed that the mechanochemical protocol affords faster Povarov reactions in comparable yields using a solvent-less environment. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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12 pages, 6265 KiB

Open AccessArticle

Efficient Regioselective Synthesis of Novel Water-Soluble 2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium Derivatives by Annulation Reactions of 8-quinolinesulfenyl Halides

by Vladimir A. Potapov, Roman S. Ishigeev and Svetlana V. Amosova

Molecules 2021, 26(4), 1116; https://doi.org/10.3390/molecules26041116 - 20 Feb 2021

Cited by 4 | Viewed by 2504

Abstract

Regioselective synthesis of novel 2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives has been developed by annulation reactions of 8-quinolinesulfenyl halides with vinyl chalcogenides (vinyl ethers, divinyl sulfide, divinyl selenide and phenyl vinyl sulfide) and tetravinyl silane. The novel reagent 8-quinolinesulfenyl bromide was [...] Read more.

Regioselective synthesis of novel 2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives has been developed by annulation reactions of 8-quinolinesulfenyl halides with vinyl chalcogenides (vinyl ethers, divinyl sulfide, divinyl selenide and phenyl vinyl sulfide) and tetravinyl silane. The novel reagent 8-quinolinesulfenyl bromide was used in the annulation reactions. The influence of the substrate structure and the nature of heteroatoms on the direction of the reactions and on product yields has been studied. The opposite regiochemistry was observed in the reactions with vinyl chalcogenides and tetravinyl silane. The obtained condensed heterocycles are novel water-soluble functionalized compounds with promising biological activity. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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31 pages, 4040 KiB

Open AccessArticle

Microwave-Assisted Synthesis of (Piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides as Potent Inhibitors of Cholinesterases: A Biochemical and In Silico Approach

by Rubina Munir, Muhammad Zia-ur-Rehman, Shahzad Murtaza, Sumera Zaib, Noman Javid, Sana Javaid Awan, Kiran Iftikhar, Muhammad Makshoof Athar and Imtiaz Khan

Molecules 2021, 26(3), 656; https://doi.org/10.3390/molecules26030656 - 27 Jan 2021

Cited by 27 | Viewed by 5803

Abstract

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer’s heterocyclic structural leads, the [...] Read more.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer’s heterocyclic structural leads, the treatment of AD requires safer hybrid therapeutics with characteristic structural and biochemical properties. In this endeavor, we herein report a microwave-assisted synthesis of a library of quinoline thiosemicarbazones endowed with a piperidine moiety, achieved via the condensation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes and (un)substituted thiosemicarbazides. The target N-heterocyclic products were isolated in excellent yields. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, ¹H- and ¹³C-NMR). Anti-Alzheimer potential of the synthesized heterocyclic compounds was evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vitro biochemical assay results revealed several compounds as potent inhibitors of both enzymes. Among them, five compounds exhibited IC₅₀ values less than 20 μM. N-(3-chlorophenyl)-2-((8-methyl-2-(piperidin-1-yl)quinolin-3-yl)methylene)hydrazine carbothioamide emerged as the most potent dual inhibitor of AChE and BChE with IC₅₀ values of 9.68 and 11.59 μM, respectively. Various informative structure–activity relationship (SAR) analyses were also concluded indicating the critical role of substitution pattern on the inhibitory efficacy of the tested derivatives. In vitro results were further validated through molecular docking analysis where interactive behavior of the potent inhibitors within the active pocket of enzymes was established. Quinoline thiosemicarbazones were also tested for their cytotoxicity using MTT assay against HepG2 cells. Among the 26 novel compounds, there were five cytotoxical and 18 showed proliferative properties. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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16 pages, 6768 KiB

Open AccessArticle

The Three-Component Synthesis of 4-Sulfonyl-1,2,3-triazoles via a Sequential Aerobic Copper-Catalyzed Sulfonylation and Dimroth Cyclization

by Max Van Hoof, Santhini Pulikkal Veettil and Wim Dehaen

Molecules 2021, 26(3), 581; https://doi.org/10.3390/molecules26030581 - 22 Jan 2021

Cited by 4 | Viewed by 3932

Abstract

4-Sulfonyl-1,2,3-triazole scaffolds possess promising bioactivities and applications as anion binders. However, these structures remain relatively unexplored and efficient synthetic procedures for their synthesis remain desirable. A practical room-temperature, aerobic copper-catalyzed three-component reaction of aromatic ketones, sodium sulfinates, and azides is reported. This procedure [...] Read more.

4-Sulfonyl-1,2,3-triazole scaffolds possess promising bioactivities and applications as anion binders. However, these structures remain relatively unexplored and efficient synthetic procedures for their synthesis remain desirable. A practical room-temperature, aerobic copper-catalyzed three-component reaction of aromatic ketones, sodium sulfinates, and azides is reported. This procedure allows for facile access to 4-sulfonyl-1,5-disubstituted-1,2,3-triazoles in yields ranging from 34 to 89%. The reaction proceeds via a sequential aerobic copper(II)chloride-catalyzed oxidative sulfonylation and the Dimroth azide–enolate cycloaddition. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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13 pages, 3046 KiB

Open AccessArticle

Helicity: A Non-Conventional Stereogenic Element for Designing Inherently Chiral Ionic Liquids for Electrochemical Enantiodifferentiation

by Francesca Fontana, Greta Carminati, Benedetta Bertolotti, Patrizia Romana Mussini, Serena Arnaboldi, Sara Grecchi, Roberto Cirilli, Laura Micheli and Simona Rizzo

Molecules 2021, 26(2), 311; https://doi.org/10.3390/molecules26020311 - 9 Jan 2021

Cited by 12 | Viewed by 2922

Abstract

Configurationally stable 5-aza[6]helicene (1) was envisaged as a promising scaffold for non-conventional ionic liquids (IL)s. It was prepared, purified, and separated into enantiomers by preparative HPLC on a chiral stationary phase. Enantiomerically pure quaternary salts of 1 with appropriate counterions were [...] Read more.

Configurationally stable 5-aza[6]helicene (1) was envisaged as a promising scaffold for non-conventional ionic liquids (IL)s. It was prepared, purified, and separated into enantiomers by preparative HPLC on a chiral stationary phase. Enantiomerically pure quaternary salts of 1 with appropriate counterions were prepared and fully characterized. N-octyl-5-aza[6]helicenium bis triflimidate (2) was tested in very small quantities as a selector in achiral IL media to perform preliminary electrochemical enantiodifferentiation experiments on the antipodes of two different chiral probes. The new organic salt exhibited outstanding enantioselection performance with respect to these probes, thus opening the way to applications in the enantioselective electroanalysis of relevant bioactive molecules. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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12 pages, 2338 KiB

Open AccessFeature PaperArticle

The Quaternization Reaction of 5-O-Sulfonates of Methyl 2,3-o-Isopropylidene-β-D-Ribofuranoside with Selected Heterocyclic and Aliphatic Amines

by Barbara Dmochowska, Rafał Ślusarz, Jarosław Chojnacki, Justyna Samaszko-Fiertek and Janusz Madaj

Molecules 2020, 25(9), 2161; https://doi.org/10.3390/molecules25092161 - 5 May 2020

Cited by 1 | Viewed by 4031

Abstract

The synthesis of N-((methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl)ammonium salts are presented. To determine the effect of the nucleophile type and outgoing group on the quaternization reaction, selected aliphatic and heterocyclic aromatic amines reacted with: methyl 2,3-O-isopropylidene-5-O-tosyl-β [...] Read more.

The synthesis of N-((methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl)ammonium salts are presented. To determine the effect of the nucleophile type and outgoing group on the quaternization reaction, selected aliphatic and heterocyclic aromatic amines reacted with: methyl 2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-triflyl-β-D-ribofuranoside were performed on a micro scale. High-resolution ¹H- and ¹³C-NMR spectral data for all new compounds were recorded. Additionally, the single-crystal X-ray diffraction analysis for methyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside and selected in silico interaction models are reported. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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20 pages, 3915 KiB

Open AccessArticle

Synthesis, Electrochemical and Spectroscopic Characterization of Selected Quinolinecarbaldehydes and Their Schiff Base Derivatives

by Jakub Wantulok, Marcin Szala, Andrea Quinto, Jacek E. Nycz, Stefania Giannarelli, Romana Sokolová, Maria Książek and Joachim Kusz

Molecules 2020, 25(9), 2053; https://doi.org/10.3390/molecules25092053 - 28 Apr 2020

Cited by 13 | Viewed by 6260

Abstract

A new approach to the synthesis of selected quinolinecarbaldehydes with carbonyl groups located at C5 and/or in C7 positions is presented in this paper in conjunction with spectroscopic characterization of the products. The classical Reimer-Tiemann, Vilsmeier-Haack and Duff aldehyde synthesis methods were compared [...] Read more.

A new approach to the synthesis of selected quinolinecarbaldehydes with carbonyl groups located at C5 and/or in C7 positions is presented in this paper in conjunction with spectroscopic characterization of the products. The classical Reimer-Tiemann, Vilsmeier-Haack and Duff aldehyde synthesis methods were compared due to their importance. Computational studies were carried out to explain the preferred selectivity of the presented formylation transformations. A carbene insertion reaction based on Reimer-Tiemann methodology is presented for making 7-bromo-8-hydroxyquinoline-5-carbaldehyde. Additionally, Duff and Vilsmeier-Haack reactions were used in the double formylation of quinoline derivatives and their analogues benzo[h]quinolin-10-ol, 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde, 8-(dimethylamino) quinoline-5,7-dicarbaldehyde and 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde. Four Schiff base derivatives of 2,6-diisopropylbenzenamine were prepared from selected quinoline-5-carbaldehydes and quinoline-7-carbaldehyde by an efficient synthesis protocol. Their properties have been characterized by a combination of several techniques: MS, HRMS, GC-MS, FTIR, electronic absorption spectroscopy and multinuclear NMR. The electrochemical properties of 8-hydroxy-quinoline-5-carbaldehyde, 6-(dimethylamino)quinoline-5-carbaldehyde and its methylated derivative were investigated, and a strong correlation between the chemical structure and obtained reduction and oxidation potentials was found. The presence of a methyl group facilitates oxidation. In contrast, the reduction potential of methylated compounds was more negative comparing to non-methylated structure. Calculations of frontier molecular orbitals supported the finding. The structures of 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde and four Schiff bases were determined by single-crystal X-ray diffraction measurements. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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25 pages, 8840 KiB

Open AccessArticle

Synthesis and Electrochemical and Spectroscopic Characterization of 4,7-diamino-1,10-phenanthrolines and Their Precursors

by Jacek E. Nycz, Jakub Wantulok, Romana Sokolova, Lukasz Pajchel, Marek Stankevič, Marcin Szala, Jan Grzegorz Malecki and Daniel Swoboda

Molecules 2019, 24(22), 4102; https://doi.org/10.3390/molecules24224102 - 13 Nov 2019

Cited by 14 | Viewed by 5228

Abstract

New approaches to the synthesis of 4,7-dichloro-1,10-phenanthrolines and their corresponding 9H-carbazol-9-yl-, 10H-phenothiazin-10-yl- and pyrrolidin-1-yl derivatives were developed. Their properties have been characterized by a combination of several techniques: MS, HRMS, GC-MS, electronic absorption spectroscopy and multinuclear NMR in both [...] Read more.

New approaches to the synthesis of 4,7-dichloro-1,10-phenanthrolines and their corresponding 9H-carbazol-9-yl-, 10H-phenothiazin-10-yl- and pyrrolidin-1-yl derivatives were developed. Their properties have been characterized by a combination of several techniques: MS, HRMS, GC-MS, electronic absorption spectroscopy and multinuclear NMR in both solution and solid state including ¹⁵N CP/MAS NMR. The structures of 5-fluoro-2,9-dimethyl-4,7-di(pyrrolidin-1-yl)-1,10-phenanthroline (5d), 4,7-di(9H-carbazol-9-yl)-9-oxo-9,10-dihydro-1,10-phenanthroline-5-carbonitrile (6a) and 4,7-di(10H-phenothiazin-10-yl)-1,10-phenanthroline-5-carbonitrile (6b) were determined by single-crystal X-ray diffraction measurements. The nucleophilic substitutions of hydrogen followed by oxidation produced compounds 6a and 6b. The electrochemical properties of selected 1,10-phenanthrolines were investigated using cyclic voltammetry and compared with commercially available reference 1,10-phenanthrolin-5-amine (5l). The spatial distribution of frontier molecular orbitals of the selected compounds has been calculated by density functional theory (DFT). It was shown that potentials of reduction and oxidation were in consistence with the level of HOMO and LUMO energies. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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Review

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54 pages, 16625 KiB

Open AccessReview

Fused 1,5-Naphthyridines: Synthetic Tools and Applications

by Carme Masdeu, Maria Fuertes, Endika Martin-Encinas, Asier Selas, Gloria Rubiales, Francisco Palacios and Concepcion Alonso

Molecules 2020, 25(15), 3508; https://doi.org/10.3390/molecules25153508 - 31 Jul 2020

Cited by 15 | Viewed by 5767

Abstract

Heterocyclic nitrogen compounds, including fused 1,5-naphthyridines, have versatile applications in the fields of synthetic organic chemistry and play an important role in the field of medicinal chemistry, as many of them have a wide range of biological activities. In this review, a wide [...] Read more.

Heterocyclic nitrogen compounds, including fused 1,5-naphthyridines, have versatile applications in the fields of synthetic organic chemistry and play an important role in the field of medicinal chemistry, as many of them have a wide range of biological activities. In this review, a wide range of synthetic protocols for the construction of this scaffold are presented. For example, Friedländer, Skraup, Semmlere-Wolff, and hetero-Diels-Alder, among others, are well known classical synthetic protocols used for the construction of the main 1,5-naphthyridine scaffold. These syntheses are classified according to the nature of the cycle fused to the 1,5-naphthyridine ring: carbocycles, nitrogen heterocycles, oxygen heterocycles, and sulphur heterocycles. In addition, taking into account the aforementioned versatility of these heterocycles, their reactivity is presented as well as their use as a ligand for metal complexes formation. Finally, those fused 1,5-naphthyridines that present biological activity and optical applications, among others, are indicated. Full article

(This article belongs to the Special Issue N-Heterocycles: Synthesis, Functionalization, Electrochemical, Spectroscopic Characterization and Mechanistic Investigation)

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