E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Topical Collection "Heterocyclic Compounds"

A topical collection in Molecules (ISSN 1420-3049). This collection belongs to the section "Organic Synthesis".

Editors

Collection Editor
Prof. Dr. Richard A. Bunce

Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74078-3071, USA
Website | E-Mail
Interests: heterocycles; antibacterial agents; anticancer agents; enzyme inhibitors; medicinal chemistry; drug discovery; drug development; synthetic methodology
Collection Editor
Prof. Dr. Philippe Belmont

School of Pharmacy, University Paris Descartes, UMR CNRS 8638, case 24. 4, avenue de l’Observatoire, 75006 Paris, France
E-Mail
Interests: heterocyclic synthesis; nitrogen-containing heterocycles; methodologies using organic or organometallic reagents; organometallic catalysis; cyclo-isomerization reactions; cyclo-functionalization reactions; benzannulation; aminobenzannulation; pi-acid metal catalysis; silver chemistry; gold chemistry; cobalt chemistry; Pauson-Khand reaction; bioactive compounds; alkaloids; kinases inhibition
Collection Editor
Prof. Dr. Wim Dehaen

Department of Chemistry, Celestijnenlaan 200F, B-3001 Leuven, Belgium
Website | E-Mail
Phone: +32 16 32 74 39
Fax: +32 16 32 79 90
Interests: organic synthesis; heterocycles; supramolecular chemistry; porphyrin analogues; natural products; helicenes
Collection Editor
Prof. Dr. Eugene Babaev

Chemistry Department, Moscow State University, GSP-3, Moscow 119991, Russia
Website | E-Mail
Interests: heterocyclic chemistry; periodic table

Topical Collection Information

Dear Colleagues,

Heterocyclic compounds are an important class of molecules in organic chemistry, due to their presence in natural products and their use in pharmaceuticals and new materials. Heterocycles are the key to biological activity in many small molecule drugs, due to their ability to hydrogen bond, alter polarity, and modulate lipophilicity at specific sites in the pathogen or host, with the overall effect of inhibiting the biological processes that lead to the programmed progressions of diseases. Similar advantages can be cited in the area of materials chemistry, as heterocycles can impart unique properties to new materials, due to their polarity, solubility, and their electronic and optical properties. In this Molecules Special Issue, entitled "Heterocyclic Compounds", we invite manuscript submissions that focus on the synthesis of natural and unnatural heterocyclic compounds and their potential uses in medicinal and materials chemistry. It is expected that most submissions will focus on nitrogen, oxygen, and sulfur heterocycles, but structures incorporating other heteroatoms will also be considered. Original research articles or reviews that discuss synthetic methodologies for preparing heterocyclic compounds, total synthesis, and structure studies of heterocycle-containing substances, as well as potential new applications to medicinal and materials chemistry, are particularly welcome.

Dr. Richard A. Bunce
Dr. Philippe Belmont
Dr. Wim Dehaen
Prof. Dr. Eugene Babaev
Collection Editors

Manuscript Submission Information

Manuscripts for the topical collection can be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on this website. The topical collection considers regular research articles, short communications and review articles. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page.

Please visit the Instructions for Authors page before submitting a manuscript. The article processing charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

  • new synthetic approaches to heterocycles
  • synthesis of heterocyclic natural products
  • biologically active heterocycles
  • medicinal studies of heterocycles
  • structure-activity relationships of drugs containing heterocycles
  • new heterocycle-based materials
  • structure-property relationships of materials containing heterocycles
  • heterocycles with unique properties
  • applications of heterocycle-based materials

Published Papers (72 papers)

2017

Jump to: 2016, 2015

Open AccessArticle Synthesis of Novel Glycerol-Derived 1,2,3-Triazoles and Evaluation of Their Fungicide, Phytotoxic and Cytotoxic Activities
Molecules 2017, 22(10), 1666; doi:10.3390/molecules22101666
Received: 1 September 2017 / Revised: 29 September 2017 / Accepted: 3 October 2017 / Published: 7 October 2017
PDF Full-text (1195 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal
[...] Read more.
The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicidal activity was assessed in vitro against Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)-cyclo-hexanol (4g) and 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency in controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a promising scaffold to be explored for the development of new agents to control C. gloeosporioides. Full article
Figures

Open AccessArticle Hydrogen-Bonding Interactions in Luminescent Quinoline-Triazoles with Dominant 1D Crystals
Molecules 2017, 22(10), 1600; doi:10.3390/molecules22101600
Received: 24 August 2017 / Revised: 14 September 2017 / Accepted: 15 September 2017 / Published: 22 September 2017
PDF Full-text (3524 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Quinoline-triazoles 2-((4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (1), 2-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (2) and 2-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (3) have been prepared with CuAAC click reactions and used as a model series to probe the relationship between lattice H-bonding interaction and crystal
[...] Read more.
Quinoline-triazoles 2-((4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (1), 2-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (2) and 2-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (3) have been prepared with CuAAC click reactions and used as a model series to probe the relationship between lattice H-bonding interaction and crystal direction of growth. Crystals of 13 are 1D tape and prism shapes that correlate with their intermolecular and solvent 1D lattice H-bonding interactions. All compounds were thermally stable up to about 200 C and blue-green emissive in solution. Full article
Figures

Open AccessArticle A Facile Oxidative Opening of the C-Ring in Luotonin A and Derivatives
Molecules 2017, 22(9), 1540; doi:10.3390/molecules22091540
Received: 7 August 2017 / Revised: 11 September 2017 / Accepted: 11 September 2017 / Published: 12 September 2017
Cited by 1 | PDF Full-text (1039 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An oxidative ring opening reaction of the central ring C in the alkaloid Luotonin A and two of its derivatives was found to occur upon heating with an excess amine and potassium carbonate in dimethylsulfoxide (DMSO) solution in the presence of air oxygen.
[...] Read more.
An oxidative ring opening reaction of the central ring C in the alkaloid Luotonin A and two of its derivatives was found to occur upon heating with an excess amine and potassium carbonate in dimethylsulfoxide (DMSO) solution in the presence of air oxygen. The structure of the novel amide-type products was elucidated and a possible mechanism for this reaction is proposed. Four of the new compounds show moderate in vitro anticancer activity towards human colon adenocarcinoma cells. Full article
Figures

Open AccessArticle Synthesis and DFT Calculations of Novel Vanillin-Chalcones and Their 3-Aryl-5-(4-(2-(dimethylamino)-ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde Derivatives as Antifungal Agents
Molecules 2017, 22(9), 1476; doi:10.3390/molecules22091476
Received: 8 August 2017 / Revised: 31 August 2017 / Accepted: 31 August 2017 / Published: 5 September 2017
PDF Full-text (4634 KB) | HTML Full-text | XML Full-text
Abstract
Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxy-benzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction
[...] Read more.
Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxy-benzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction was carried out in formic acid. The antifungal activity of both series of compounds against eight fungal species was determined. In general, chalcone derivatives 4 showed better activities than pyrazolines 5 against all tested fungi. None of the compounds 4ag and 5ag showed activity against the three Aspergillus spp. In contrast, most of the compounds 4 showed moderate to high activities against three dermatophytes (MICs 31.25–62.5 µg/mL), being 4a followed by 4c the most active structures. Interestingly, 4a and 4c possess fungicidal rather than fungistatic activities, with MFC values between 31.25 and 62.5 μg/mL. The comparison of the percentages of inhibition of C. neoformans by the most active compounds 4, allowed us to know the role played by the different substituents of the chalcones’ A-ring. Also the most anti-cryptococcal compounds 4ac and 4g, were tested in a second panel of five clinical C. neoformans strains in order to have an overview of their inhibition capacity not only of standardized but also of clinical C. neoformans strains. DFT calculations showed that the electrophilicity is the main electronic property to explain the differences in antifungal activities for the synthesized chalcones and pyrazolines compounds. Furthermore, a quantitative reactivity analysis showed that electron-withdrawing substituted chalcones presented the higher electrophilic character and hence, the greater antifungal activities among compounds of series 4. Full article
Figures

Open AccessArticle Voltammetric Study of Some 3-Aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide Derivatives with Anti-Tumor Activities
Molecules 2017, 22(9), 1442; doi:10.3390/molecules22091442
Received: 9 August 2017 / Revised: 28 August 2017 / Accepted: 29 August 2017 / Published: 31 August 2017
PDF Full-text (3960 KB) | HTML Full-text | XML Full-text
Abstract
The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible
[...] Read more.
The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible or quasireversible and is attributed to reduction of the N-oxide moiety to form a radical anion. The second reduction of the diazine ring was found to be irreversible. Compounds containing a nitro group on the 3-phenyl ring also exhibited a reduction process that may be attributed to that group. There was good correlation between molecular structure and reduction potential, with reduction being facilitated by an enhanced net positive charge at the electroactive site created by electron withdrawing substituents. Additionally, the reduction potential was calculated using two common basis sets, 6-31g and lanl2dz, for five of the test molecules. There was a strong correlation between the computational data and the experimental data, with the exception of the derivative containing the nitro functionality. No relationship between the experimentally measured reduction potentials and reported cytotoxic activities was evident upon comparison of the data. Full article
Figures

Open AccessArticle Pyrene-Phosphonate Conjugate: Aggregation-Induced Enhanced Emission, and Selective Fe3+ Ions Sensing Properties
Molecules 2017, 22(9), 1417; doi:10.3390/molecules22091417
Received: 19 July 2017 / Revised: 17 August 2017 / Accepted: 21 August 2017 / Published: 29 August 2017
PDF Full-text (3540 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE) properties in water/acetonitrile (ACN) solutions. Dynamic light
[...] Read more.
A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE) properties in water/acetonitrile (ACN) solutions. Dynamic light scattering (DLS) characterization revealed that the aggregates of receptor 1 at 80% water fraction have an average size of ≈142 nm. Field emission scanning electron microscopy (FE-SEM) analysis confirmed the formation of spherical aggregates upon solvent evaporation. The sensing properties of receptor 1 were investigated by UV-vis, fluorescence emission spectroscopy, and other optical methods. Among the tested metal ions, receptor 1 is capable of recognizing the Fe3+ ion selectively. The changes in spectral measurements were explained on the basis of complex formation. The composition of receptor 1 and Fe3+ ions was determined by using Job’s plot and found to be 1:1. The receptor 1–Fe3+ complex showed a reversible UV-vis response in the presence of EDTA. Full article
Figures

Open AccessArticle Covalent Porphyrin Hybrids Linked with Dipyrrin, Bidipyrrin or Thiacorrole
Molecules 2017, 22(9), 1400; doi:10.3390/molecules22091400
Received: 3 August 2017 / Revised: 19 August 2017 / Accepted: 20 August 2017 / Published: 23 August 2017
PDF Full-text (2137 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin
[...] Read more.
Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin nickel complex 3 was successfully obtained in a high yield by the oxidation of porphyrinyl dipyrromethane 2 and subsequent coordination. Further oxidative coupling reactions of 3 afforded por-bidipyrrin-por hybrid 4. Interestingly, an unexpected methoxy por-bidipyrrin-por hybrid 6 was generated by treating 4 with FeCl3 in CH2Cl2/MeOH and subsequent coordination. In addition to open chain hybrids, an aromatic scaffold hybrid por-thiacorrole-por 8 was synthesized by treating porphyrinyl dibromo-dipyrrin nickel complex 7 with Na2S·9H2O. A series of porphyrin hybrids offers a new approach for π-conjugated molecules. Full article
Figures

Open AccessArticle Tetrabutylammonium Iodide–Promoted Thiolation of Oxindoles Using Sulfonyl Chlorides as Sulfenylation Reagents
Molecules 2017, 22(8), 1208; doi:10.3390/molecules22081208
Received: 11 July 2017 / Revised: 26 July 2017 / Accepted: 28 July 2017 / Published: 1 August 2017
PDF Full-text (1707 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
3-Sulfanyloxindoles were synthesised by triphenylphosphine-mediated transition-metal-free thiolation of oxindoles using sulfonyl chlorides as sulfenylation reagents. The above reaction was promoted by iodide anions, which was ascribed to the in situ conversion of sulfenyl chlorides into the more reactive sulfenyl iodides. Moreover, the thiolation
[...] Read more.
3-Sulfanyloxindoles were synthesised by triphenylphosphine-mediated transition-metal-free thiolation of oxindoles using sulfonyl chlorides as sulfenylation reagents. The above reaction was promoted by iodide anions, which was ascribed to the in situ conversion of sulfenyl chlorides into the more reactive sulfenyl iodides. Moreover, the thiolation of 3-aryloxindoles was facilitated by bases. The use of a transition-metal-free protocol, readily available reagents, and mild reaction conditions make this protocol more practical for preparing 3-sulfanyloxindoles than traditional methods. Full article
Figures

Open AccessArticle Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles
Molecules 2017, 22(7), 1211; doi:10.3390/molecules22071211
Received: 7 June 2017 / Revised: 8 July 2017 / Accepted: 17 July 2017 / Published: 20 July 2017
PDF Full-text (1490 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d
[...] Read more.
A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC50 values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC50 = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results. Full article
Figures

Figure 1

Open AccessArticle Study on the Alkylation Reactions of N(7)-Unsubstituted 1,3-Diazaoxindoles
Molecules 2017, 22(5), 846; doi:10.3390/molecules22050846
Received: 9 April 2017 / Revised: 13 May 2017 / Accepted: 16 May 2017 / Published: 19 May 2017
PDF Full-text (4430 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were
[...] Read more.
The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were synthesized from the C(5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C(5) position possible with reasonable selectivity, without affecting the N(7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized. Full article
Figures

Open AccessArticle One-Flask Synthesis of Pyrazolo[3,4-d]pyrimidines from 5-Aminopyrazoles and Mechanistic Study
Molecules 2017, 22(5), 820; doi:10.3390/molecules22050820
Received: 18 March 2017 / Revised: 11 May 2017 / Accepted: 11 May 2017 / Published: 16 May 2017
PDF Full-text (1221 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr3. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions
[...] Read more.
A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr3. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions thus involved Vilsmeier amidination, imination reactions, and the sequential intermolecular heterocyclization. To study the reaction mechanism, a series of 4-formyl-1,3-diphenyl-1H-pyrazol-5-yl-N,N-disubstituted formamidines, which were conceived as the chemical equivalent of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl-formamidine, were prepared and successfully converted into pyrazolo[3,4-d]pyrimidines. The experiments demonstrated that the reaction intermediates were the chemical equivalents of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl)formamidines. The rate of the reaction could be described as being proportional to the reactivity of amine reactants during intermolecular heterocyclization, especially when hexamethyldisilazane was used. Full article
Figures

Open AccessArticle Ortho-Nitro Effect on the Diastereoselective Control in Sulfa-Staudinger and Staudinger Cycloadditions
Molecules 2017, 22(5), 784; doi:10.3390/molecules22050784
Received: 6 February 2017 / Revised: 8 May 2017 / Accepted: 9 May 2017 / Published: 12 May 2017
Cited by 2 | PDF Full-text (1683 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions deliver cis-β-sultams in considerable amounts, together with the predominant trans
[...] Read more.
The ortho-nitro effect was discovered in sulfa-Staudinger cycloadditions of ethoxycarbonylsulfene with linear imines. When an ortho-nitro group is present at the C-aryl substituents of linear imines, the sulfa-Staudinger cycloadditions deliver cis-β-sultams in considerable amounts, together with the predominant trans-β-sultams. In other cases, the above sulfa-Staudinger cycloadditions give rise to trans-β-sultams exclusively. Further mechanistic rationalization discloses that the ortho-nitro effect is attributed to its strong electron-withdrawing inductive effect. Similarly, the ortho-nitro effect also exists in Staudinger cycloadditions of ethoxycarbonyl ketene with the imines. The current research provides further insights into the diastereoselective control in sulfa-Staudinger and Staudinger cycloadditions. Full article
Figures

Open AccessArticle Rhodium(I)-Complexes Catalyzed 1,4-Conjugate Addition of Arylzinc Chlorides to N-Boc-4-pyridone
Molecules 2017, 22(5), 723; doi:10.3390/molecules22050723
Received: 15 March 2017 / Revised: 27 April 2017 / Accepted: 27 April 2017 / Published: 1 May 2017
PDF Full-text (885 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N-Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C2H4)2]2 and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition
[...] Read more.
Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N-Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C2H4)2]2 and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition reactions of arylzinc chlorides to N-Boc-4-pyridone. A broad scope of arylzinc reagents with both electron-withdrawing and electron-donating substituents on the aromatic ring successfully underwent 1,4-conjugate addition to N-Boc-4-pyridone to afford versatile 1,4-adducts 2-substituted-2,3-dihydropyridones in good to excellent yields (up to 91%) and excellent ee (up to 96%) when (S)-BINAP was used as chiral ligand. Full article
Figures

Open AccessArticle Reactions of 5-Indolizyl Lithium Compounds with Some Bielectrophiles
Molecules 2017, 22(4), 661; doi:10.3390/molecules22040661
Received: 3 March 2017 / Revised: 9 April 2017 / Accepted: 17 April 2017 / Published: 20 April 2017
PDF Full-text (1082 KB) | HTML Full-text | XML Full-text
Abstract
Abstract: Indolizyl-5-lithium anions react with succinic and phtalic anhidrides giving 1,4-keto acids, with oxallyl chloride giving 1,2-diketone, and with ethyl pyruvate giving 1,2-hydroxyacid. However, with α-halocarbonyl compounds, they react in different ways, forming the products of selective bromination at C-5 (with α-bromo
[...] Read more.
Abstract: Indolizyl-5-lithium anions react with succinic and phtalic anhidrides giving 1,4-keto acids, with oxallyl chloride giving 1,2-diketone, and with ethyl pyruvate giving 1,2-hydroxyacid. However, with α-halocarbonyl compounds, they react in different ways, forming the products of selective bromination at C-5 (with α-bromo ketones and esters of α-bromo acids) and 5-chloroacetyl indolizines. Full article
Figures

Open AccessArticle Molecular Hybridization-Guided One-Pot Multicomponent Synthesis of Turmerone Motif-Fused 3,3′-Pyrrolidinyl-dispirooxindoles via a 1,3-Dipolar Cycloaddition Reaction
Molecules 2017, 22(4), 645; doi:10.3390/molecules22040645
Received: 23 March 2017 / Revised: 11 April 2017 / Accepted: 13 April 2017 / Published: 17 April 2017
Cited by 1 | PDF Full-text (9131 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles 3–5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products
[...] Read more.
Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles 3–5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products bearing four or three consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable application of this method was for the design of new hybrid architectures for biological screening through the adequate fusion of these sub-units of turmerone and 3,3′-pyrrolidinyl-dispirooxindole, generating drug-like molecules. Full article
Figures

Open AccessArticle Consecutive One-Pot versus Domino Multicomponent Approaches to 3-(Diarylmethylene)oxindoles
Molecules 2017, 22(3), 503; doi:10.3390/molecules22030503
Received: 27 February 2017 / Revised: 9 March 2017 / Accepted: 17 March 2017 / Published: 22 March 2017
Cited by 1 | PDF Full-text (4684 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Based on consecutive one-pot conditions combining three palladium-catalyzed reactions (Sonogashira, Heck and Suzuki-Miyaura reactions), a more efficient domino multicomponent method has been successfully developed to access a wide variety of 3-(diarylmethylene)oxindoles. Microwave irradiation and use of a silver salt were the most important
[...] Read more.
Based on consecutive one-pot conditions combining three palladium-catalyzed reactions (Sonogashira, Heck and Suzuki-Miyaura reactions), a more efficient domino multicomponent method has been successfully developed to access a wide variety of 3-(diarylmethylene)oxindoles. Microwave irradiation and use of a silver salt were the most important factors to achieve high yields and stereoselectivity. Full article
Figures

Open AccessArticle Design of New Benzo[h]chromene Derivatives: Antitumor Activities and Structure-Activity Relationships of the 2,3-Positions and Fused Rings at the 2,3-Positions
Molecules 2017, 22(3), 479; doi:10.3390/molecules22030479
Received: 27 January 2017 / Revised: 11 March 2017 / Accepted: 13 March 2017 / Published: 18 March 2017
PDF Full-text (2384 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel 4H-benzo[h]chromenes 4, 611, 13, 14; 7H-benzo[h]chromeno[2,3-d]pyrimidines 1518, 20, and 14H-benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives
[...] Read more.
A series of novel 4H-benzo[h]chromenes 4, 611, 13, 14; 7H-benzo[h]chromeno[2,3-d]pyrimidines 1518, 20, and 14H-benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 19ae, 24 was prepared. The structures of the synthesized compounds were characterized on the basis of their spectral data. Some of the target compounds were examined for their antiproliferative activity against three cell lines; breast carcinoma (MCF-7), human colon carcinoma (HCT-116) and hepatocellular carcinoma (HepG-2). The cytotoxic behavior has been tested using MTT assay and the inhibitory activity was referenced to three standard anticancer drugs: vinblastine, colchicine and doxorubicin. The bioassays demonstrated that some of the new compounds exerted remarkable inhibitory effects as compared to the standard drugs on the growth of the three tested human tumor cell lines. The structure–activity relationships (SAR) study highlights that the antitumor activity of the target compounds was significantly affected by the lipophilicity of the substituent at 2- or 3- and fused rings at the 2,3-positions. Full article
Figures

Figure 1

Open AccessArticle Facial Regioselective Synthesis of Novel Bioactive Spiropyrrolidine/Pyrrolizine-Oxindole Derivatives via a Three Components Reaction as Potential Antimicrobial Agents
Molecules 2017, 22(3), 357; doi:10.3390/molecules22030357
Received: 9 January 2017 / Revised: 19 February 2017 / Accepted: 24 February 2017 / Published: 26 February 2017
Cited by 1 | PDF Full-text (554 KB) | HTML Full-text | XML Full-text
Abstract
This article presents the synthesis of new derivatives of spirooxindole-spiropiperidinone- pyrrolidines 6aj and spirooxindole-spiropiperidinone-pyrrolizines 8aj, through a 1,3-dipolar cycloaddition reaction of azomethineylides generated from isatin, sarcosine, and l-proline, through a decarboxylative route with dipolarophile 4aj. All
[...] Read more.
This article presents the synthesis of new derivatives of spirooxindole-spiropiperidinone- pyrrolidines 6aj and spirooxindole-spiropiperidinone-pyrrolizines 8aj, through a 1,3-dipolar cycloaddition reaction of azomethineylides generated from isatin, sarcosine, and l-proline, through a decarboxylative route with dipolarophile 4aj. All of the newly synthesized compounds were evaluated for their antimicrobial activities and their minimum inhibitory concentration (MIC) against most of the test organisms. The tested compounds displayed excellent activity against all of the tested microorganisms. Full article
Figures

Scheme 1

Open AccessArticle Diastereoselective Synthesis of Spirocyclopropanes under Mild Conditions via Formal [2 + 1] Cycloadditions Using 2,3-Dioxo-4-benzylidene-pyrrolidines
Molecules 2017, 22(2), 328; doi:10.3390/molecules22020328
Received: 16 January 2017 / Revised: 14 February 2017 / Accepted: 16 February 2017 / Published: 22 February 2017
Cited by 1 | PDF Full-text (2243 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A highly diastereoselective cyclopropanation of cyclic enones with sulfur ylides was developed under catalyst-free conditions, producing multifunctional spirocyclopropanes in generally excellent yields (up to 99% yield and >99:1 d.r.). The asymmetric version of this method was realized by using an easily available chiral
[...] Read more.
A highly diastereoselective cyclopropanation of cyclic enones with sulfur ylides was developed under catalyst-free conditions, producing multifunctional spirocyclopropanes in generally excellent yields (up to 99% yield and >99:1 d.r.). The asymmetric version of this method was realized by using an easily available chiral sulfur ylide, affording products with moderate to good stereoselectivity. Full article
Figures

Open AccessArticle Cytotoxicity and Antioxidant Potential of Novel 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole Derivatives
Molecules 2017, 22(2), 260; doi:10.3390/molecules22020260
Received: 4 January 2017 / Revised: 1 February 2017 / Accepted: 7 February 2017 / Published: 9 February 2017
Cited by 3 | PDF Full-text (5184 KB) | HTML Full-text | XML Full-text
Abstract
Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC50
[...] Read more.
Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC50: 11.6 μM (1), and 12.4 μM (3)] and HeLa [IC50: 22.4 μM (1) and 19.4μM (3)] cell lines is reported. Their antioxidant potential was evaluated by spectrophotometric method, using DPPH radical or Fe (TPTZ)3+ complex, and EPR spectroscopy, therefore the compounds 1 and 3 showed remarkable antioxidant activity simultaneously with a cytotoxic effect on A2780 and HeLa cell lines. Furthermore, based on theoretical quantum chemical calculation, the present study analyzed the chemoselectivity of the hydrogen extraction from the indolyl-hydrazinil-thiazoles in reaction with free radicals. Full article
Figures

Figure 1

2016

Jump to: 2017, 2015

Open AccessArticle Facile Synthesis for Benzo-1,4-Oxazepine Derivatives by Tandem Transformation of C-N Coupling/C-H Carbonylation
Molecules 2017, 22(1), 53; doi:10.3390/molecules22010053
Received: 21 November 2016 / Revised: 22 December 2016 / Accepted: 28 December 2016 / Published: 30 December 2016
PDF Full-text (6085 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A tandem transformation of C-N coupling/C-H carbonylation has been developed for the synthesis of benzo-1,4-oxazepine pharmaceutically derivatives. Notably, this reaction was accomplished by various phenylamine with ally halides under carbon dioxide atmosphere employing 2-(2-dimethylamino-vinyl)-1H-inden-1-olcatalyzed. Furthermore, under the optimized conditions, various benzo-1,4-oxazepine
[...] Read more.
A tandem transformation of C-N coupling/C-H carbonylation has been developed for the synthesis of benzo-1,4-oxazepine pharmaceutically derivatives. Notably, this reaction was accomplished by various phenylamine with ally halides under carbon dioxide atmosphere employing 2-(2-dimethylamino-vinyl)-1H-inden-1-olcatalyzed. Furthermore, under the optimized conditions, various benzo-1,4-oxazepine derivatives were obtained in good yields. Finally, a plausible CuI/CuIII mechanism of C-N coupling/C-H carbonylation transformation was proposed. Full article
Figures

Scheme 1

Open AccessArticle Novel 2,3-Dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones: Synthesis and Biological Evaluation
Molecules 2017, 22(1), 55; doi:10.3390/molecules22010055
Received: 8 December 2016 / Revised: 21 December 2016 / Accepted: 28 December 2016 / Published: 30 December 2016
PDF Full-text (1338 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum.
[...] Read more.
Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The title compounds were prepared via PdCl2-mediated endo-dig cyclization of 2-aryl-8-(arylethynyl)-6-bromo-2,3-dihydroquinazolin-4(1H)-ones. The latter were prepared, in turn, via initial Sonogashira cross-coupling of 2-amino-5-bromo-3-iodobenzamide with aryl acetylenes followed by boric acid-mediated cyclocondensation of the intermediate 2-amino-3-(arylethynyl)-5-bromobenzamides with benzaldehyde derivatives. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones 4ak were evaluated for potential in vitro cytotoxicity against the breast (MCF-7), melanoma (B16) and endothelioma (sEnd.2) cell lines. All of the compounds except 4h and 4i were found to be inactive against the three cancer cell lines. Compound 4h substituted with a 4-methoxyphenyl and 4-fluorophenyl groups at the 3- and 5-positions was found to exhibit significant cytotoxicity against the three cancer cell lines. The presence of phenyl and 3-chlorophenyl groups at the 3- and 5-posiitons of the pyrroloquinazolinone 4i, on the other hand, resulted in significant cytotoxicity against vascular tumour endothelial cells (sEnd.2), but reduced activity against the melanoma (B16) and breast cancer (MCF-7) cells except at higher concentrations. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones 4al were found to be inactive against the chloroquine sensitive 3D7 strain of Plasmodium falciparum. Full article
Figures

Open AccessArticle A Metal-Free Regioselective Multicomponent Approach for the Synthesis of Free Radical Scavenging Pyrimido-Fused Indazoles and Their Fluorescence Studies
Molecules 2016, 21(11), 1571; doi:10.3390/molecules21111571
Received: 23 September 2016 / Revised: 8 November 2016 / Accepted: 11 November 2016 / Published: 18 November 2016
Cited by 2 | PDF Full-text (2326 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study deals with a new and efficient metal-free regioselective synthesis of pyrimido-fused indazoles with nitrogen ring junction motifs. We have developed a metal-free domino type reaction between 3-aminoindazole, aryl aldehydes and aceotophenones in the presence of KOH/DMF that leads to pyrimido[1,2-b
[...] Read more.
This study deals with a new and efficient metal-free regioselective synthesis of pyrimido-fused indazoles with nitrogen ring junction motifs. We have developed a metal-free domino type reaction between 3-aminoindazole, aryl aldehydes and aceotophenones in the presence of KOH/DMF that leads to pyrimido[1,2-b]indazole analogues. Response Surface Methodology (RSM) coupled with a Box-Behnken design (BBD) were utilized for exploring the effect of base used (A), temperature of reaction (B) and (C), reaction time. This approach can allow access to a variety of pyrimidoindazole fluorophores and related compounds. The compound N,N-dimethyl-4-(2-phenylpyrimido[1,2-b]indazol-4-yl)aniline (4e) displays the maximum fluorescence intensity at 518 nm and shows a fluorescence quantum yield of 0.068. The synthesized pyramido-fused indazoles have been evaluated for their free radical scavenging activity and compound 4f showed good antioxidant activity. Full article
Figures

Figure 1

Open AccessArticle Practical and Metal-Free Synthesis of Novel Enantiopure Amides Containing the Potentially Bioactive 5-Nitroimidazole Moiety
Molecules 2016, 21(11), 1472; doi:10.3390/molecules21111472
Received: 30 September 2016 / Revised: 26 October 2016 / Accepted: 28 October 2016 / Published: 4 November 2016
Cited by 1 | PDF Full-text (1077 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl–protected amine
[...] Read more.
We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl–protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles. Full article
Figures

Figure 1

Open AccessArticle Structural Characterization and Antimicrobial Activities of 7H-Benzo[h]chromeno[2,3-d]pyrimidine and 14H-Benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c] pyrimidine Derivatives
Molecules 2016, 21(11), 1450; doi:10.3390/molecules21111450
Received: 30 September 2016 / Revised: 22 October 2016 / Accepted: 28 October 2016 / Published: 1 November 2016
Cited by 1 | PDF Full-text (2567 KB) | HTML Full-text | XML Full-text
Abstract
Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7ao, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8ab
[...] Read more.
Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7ao, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8ab and 3-ethoxycarbonyl-14-(4-halophenyl)-12-methoxy-14H-benzo-[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-one derivatives 12ab. The structure of these novel compounds were confirmed using IR, 1H- and 13C-NMR as well as MS spectroscopy. The new compounds were evaluated in vitro for their antimicrobial activity and it was demonstrated that 7H-benzochromenopyrimidine and derivatives of 14H-benzochromenotriazolopyrimidine exhibited the most promising antibacterial activities compared to the reference antimicrobial agents. The structure activity relationship (SAR) studies of the target compounds agreed with the in vitro essays and confirmed higher potent antimicrobial activity against some of the tested microorganisms. Full article
Figures

Figure 1

Open AccessArticle Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines
Molecules 2016, 21(10), 1366; doi:10.3390/molecules21101366
Received: 30 August 2016 / Revised: 30 September 2016 / Accepted: 6 October 2016 / Published: 14 October 2016
PDF Full-text (2636 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps.
[...] Read more.
Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps. The 4-anilinoquinazolines were evaluated for potential cytotoxicity against three cancer cell lines, namely, human breast adenocarcinoma (MCF-7) cells, human cervical cancer (HeLa) and human lung cancer (A549) cells. The most active compounds, 2b, 2c, 3c, 4a, 4c and 5a, were found to be more selective against the MCF-7 and HeLa cell lines than the human lung carcinoma (A549) cells. We selected compounds 2c, 3c and 7a as representatives for further evaluation for potential to induce apoptosis and/or necrotic properties in the three cancer cell lines. Compound 2c induced apoptosis of MCF-7 cells through cell membrane alteration. Treatment of Hela and A549 cell lines with compounds 3c and 7a, respectively, led to caspase-3 activation in both cell lines. Compound 3c, on the other hand, caused more necrosis than apoptosis induction in the membrane alteration assay. Full article
Figures

Open AccessCommunication Nucleophilic Substitution on 2-Monosubstituted Quinoxalines Giving 2,3-Disubstituted Quinoxalines: Investigating the Effect of the 2-Substituent
Molecules 2016, 21(10), 1304; doi:10.3390/molecules21101304
Received: 30 August 2016 / Revised: 15 September 2016 / Accepted: 23 September 2016 / Published: 30 September 2016
PDF Full-text (1033 KB) | HTML Full-text | XML Full-text
Abstract
An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields.
[...] Read more.
An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields. 2-Monosubstituted quinoxalines bearing a phenyl and butyl substituent reacted readily with alkyl-, aryl-, heteroaryl- and alkynyl- nucluephiles, giving di-substituted quinoxalines. 2-Monosubstituted quinoxalines bearing an amine and alkynyl substituent only reacted with alkyl nucleophiles. Oxidative rearomatization to give 2,3-disubstituted quinoxaline products occurred in atmospheric O2. Full article
Figures

Open AccessArticle Optimized Conditions for Passerini-Smiles Reactions and Applications to Benzoxazinone Syntheses
Molecules 2016, 21(9), 1257; doi:10.3390/molecules21091257
Received: 27 July 2016 / Revised: 13 September 2016 / Accepted: 13 September 2016 / Published: 21 September 2016
PDF Full-text (6159 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between
[...] Read more.
Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between electron-poor phenols, isocyanides, and carbonyl derivatives. These new conditions have been applied to several synthetic strategies towards benzoxazinones. Full article
Figures

Open AccessArticle Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and Pyrimido[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines
Molecules 2016, 21(8), 1072; doi:10.3390/molecules21081072
Received: 25 June 2016 / Revised: 9 August 2016 / Accepted: 10 August 2016 / Published: 17 August 2016
Cited by 2 | PDF Full-text (1615 KB) | HTML Full-text | XML Full-text
Abstract
A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H)-diones in the presence of triethylamine. The structures of the newly
[...] Read more.
A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H)-diones in the presence of triethylamine. The structures of the newly synthesized compounds were established based on their spectral data, elemental analyses and alternative synthetic routes whenever possible. Also, the newly synthesized compounds were screened for their antimicrobial activity against various microorganisms. Full article
Figures

Scheme 1

Open AccessReview Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives
Molecules 2016, 21(8), 1032; doi:10.3390/molecules21081032
Received: 17 June 2016 / Revised: 29 July 2016 / Accepted: 29 July 2016 / Published: 9 August 2016
Cited by 1 | PDF Full-text (13225 KB) | HTML Full-text | XML Full-text
Abstract
This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc.
[...] Read more.
This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc. Green syntheses and solvent-free procedures have been introduced whenever possible. The syntheses discussed herein have been selected to illustrate the huge potential of microwave in the synthesis of highly functionalized molecules with potential therapeutic applications, in high yields, enhanced reaction rates and increased chemoselectivity, compared to conventional methods. More than 100 references from the recent literature are listed in this review. Full article
Figures

Figure 1

Open AccessReview Recent Advances in Metal-Free Quinoline Synthesis
Molecules 2016, 21(8), 986; doi:10.3390/molecules21080986
Received: 27 June 2016 / Revised: 21 July 2016 / Accepted: 22 July 2016 / Published: 29 July 2016
Cited by 12 | PDF Full-text (12785 KB) | HTML Full-text | XML Full-text
Abstract
The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes.
[...] Read more.
The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes. Quinolines were first synthesized in 1879, and since then a multitude of synthetic routes have been developed. Many of these methods, such as the Skraup, Doebner–Von Miller, and Friedlander quinoline syntheses, are well-known but suffer from inefficiency, harsh reaction conditions, and toxic reagents. This review focuses on recent transition metal-free processes toward these important heterocycles, including both novel routes and modifications to established methods. For example, variations on the Skraup method include microwave irradiation, ionic liquid media, and novel annulation partners, all of which have shown increased reaction efficiency and improved yield of the heteroring-unsubstituted quinoline products. Similarly, modifications to other synthetic routes have been implemented, with the quinoline products displaying a wide variety of substitution patterns. Full article
Figures

Open AccessArticle Synthesis and Spectral Characterization of Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives
Molecules 2016, 21(8), 967; doi:10.3390/molecules21080967
Received: 28 June 2016 / Revised: 19 July 2016 / Accepted: 20 July 2016 / Published: 23 July 2016
PDF Full-text (753 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A simple synthetic route affording 27%–85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The 1H- and 13C-NMR spectra
[...] Read more.
A simple synthetic route affording 27%–85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The 1H- and 13C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity (HMBC) NMR spectra. Full article
Figures

Open AccessArticle Synthesis of New 3-Heteroarylindoles as Potential Anticancer Agents
Molecules 2016, 21(7), 929; doi:10.3390/molecules21070929
Received: 25 May 2016 / Revised: 8 July 2016 / Accepted: 12 July 2016 / Published: 16 July 2016
Cited by 4 | PDF Full-text (1552 KB) | HTML Full-text | XML Full-text
Abstract
2-(3-(1H-Indol-3-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-substituted-5-(substituted diazenyl)thiazoles and 2-(1H-indol-3-yl)-9-substituted-4,7-disubstituted pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(7H)-ones were synthesized via reaction of hydrazonoyl halides with each of 3-(1H-indol-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide and 7-(1H-indol-3-yl)-2- thioxo-5-substituted-2,3-dihydropyrido[2,3-d]pyrimidin-4(1
[...] Read more.
2-(3-(1H-Indol-3-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-substituted-5-(substituted diazenyl)thiazoles and 2-(1H-indol-3-yl)-9-substituted-4,7-disubstituted pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(7H)-ones were synthesized via reaction of hydrazonoyl halides with each of 3-(1H-indol-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide and 7-(1H-indol-3-yl)-2- thioxo-5-substituted-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones, respectively. Also, hydrazonoyl halides were reacted with N’-(1-(1H-indol-3-yl)ethylidene)-2-cyanoacetohydrazide to afford 1,3,4-thiadiazole derivatives. Structures of the new synthesis were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Fifteen of the new compounds have been evaluated for their antitumor activity against the MCF-7 human breast carcinoma cell line. The results indicated that many of the tested compounds showed moderate to high anticancer activity when compared with doxorubicin as a reference drug. Full article
Figures

Open AccessArticle Dyeing of Polyester with Disperse Dyes: Part 2. Synthesis and Dyeing Characteristics of Some Azo Disperse Dyes for Polyester Fabrics
Molecules 2016, 21(7), 855; doi:10.3390/molecules21070855
Received: 22 May 2016 / Revised: 13 June 2016 / Accepted: 24 June 2016 / Published: 29 June 2016
Cited by 3 | PDF Full-text (713 KB) | HTML Full-text | XML Full-text
Abstract
The goal of this study was to utilize carrier for accelerating the rate of dyeing not only to enhance dyeing of polyester fabrics dyed with disperse dyes 3a,b, but also to save energy. Both the color strength expressed as dye
[...] Read more.
The goal of this study was to utilize carrier for accelerating the rate of dyeing not only to enhance dyeing of polyester fabrics dyed with disperse dyes 3a,b, but also to save energy. Both the color strength expressed as dye uptake and the fastness properties of the dyed fabrics were evaluated. Full article
Figures

Open AccessArticle Dual Behavior of Iodine Species in Condensation of Anilines and Vinyl Ethers Affording 2-Methylquinolines
Molecules 2016, 21(7), 827; doi:10.3390/molecules21070827
Received: 10 May 2016 / Revised: 15 June 2016 / Accepted: 21 June 2016 / Published: 25 June 2016
PDF Full-text (6782 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A metal-free, mild and efficient method for the synthesis of 2-methylquinolines was successfully developed by condensation of anilines with vinyl ethers in the presence of catalytic amount of iodine. Modification of both pyridine and benzene moieties was easily achieved by changing only the
[...] Read more.
A metal-free, mild and efficient method for the synthesis of 2-methylquinolines was successfully developed by condensation of anilines with vinyl ethers in the presence of catalytic amount of iodine. Modification of both pyridine and benzene moieties was easily achieved by changing only the vinyl ether and aniline. In this reaction, the iodine species was revealed to show dual behavior; molecular iodine serves as an oxidant, while its reduced form, hydrogen iodide, activates the vinyl ether. The redox reaction between these iodine species enables the use of a catalytic amount of iodine in this synthetic method. Full article
Figures

Open AccessArticle Synthesis of Bioactive 2-(Arylamino)thiazolo[5,4-f]-quinazolin-9-ones via the Hügershoff Reaction or Cu- Catalyzed Intramolecular C-S Bond Formation
Molecules 2016, 21(6), 794; doi:10.3390/molecules21060794
Received: 22 April 2016 / Revised: 12 June 2016 / Accepted: 13 June 2016 / Published: 18 June 2016
Cited by 4 | PDF Full-text (7280 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A library of thirty eight novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives (series 8, 10, 14 and 17) was prepared via the Hügershoff reaction and a Cu catalyzed intramolecular C-S bond formation, helped by microwave-assisted technology when required. The efficient
[...] Read more.
A library of thirty eight novel thiazolo[5,4-f]quinazolin-9(8H)-one derivatives (series 8, 10, 14 and 17) was prepared via the Hügershoff reaction and a Cu catalyzed intramolecular C-S bond formation, helped by microwave-assisted technology when required. The efficient multistep synthesis of the key 6-amino-3-cyclopropylquinazolin-4(3H)-one (3) has been reinvestigated and performed on a multigram scale from the starting 5-nitroanthranilic acid. The inhibitory potency of the final products was evaluated against five kinases involved in Alzheimer’s disease and showed that some molecules of the 17 series described in this paper are particularly promising for the development of novel multi-target inhibitors of kinases. Full article
Figures

Open AccessReview Synthesis of Linearly Fused Benzodipyrrole Based Organic Materials
Molecules 2016, 21(6), 785; doi:10.3390/molecules21060785
Received: 20 May 2016 / Revised: 10 June 2016 / Accepted: 13 June 2016 / Published: 17 June 2016
Cited by 3 | PDF Full-text (11078 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this review is to give an overview of the synthetic methods to prepare different indolo[3,2-b]carbazoles and similar systems with a potential use in electro-optical devices such as OLEDs (organic light emitting diode), OPVs (organic photovoltaic) and OFETs (organic
[...] Read more.
The objective of this review is to give an overview of the synthetic methods to prepare different indolo[3,2-b]carbazoles and similar systems with a potential use in electro-optical devices such as OLEDs (organic light emitting diode), OPVs (organic photovoltaic) and OFETs (organic field effect transistor). Some further modifications to the core units and their implications for specific applications are also discussed. Full article
Open AccessArticle Design, Synthesis and Antifungal Activity of Novel Benzofuran-Triazole Hybrids
Molecules 2016, 21(6), 732; doi:10.3390/molecules21060732
Received: 20 April 2016 / Revised: 27 May 2016 / Accepted: 1 June 2016 / Published: 7 June 2016
Cited by 2 | PDF Full-text (1315 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic
[...] Read more.
A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic fungi. The result indicated that the target compounds exhibited moderate to satisfactory activity. Furthermore, molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation. Full article
Open AccessArticle Synthesis of Novel UV Absorbers Bisindolylmethanes and Investigation of Their Applications on Cotton-Based Textile Materials
Molecules 2016, 21(6), 718; doi:10.3390/molecules21060718
Received: 14 April 2016 / Revised: 25 May 2016 / Accepted: 27 May 2016 / Published: 3 June 2016
Cited by 2 | PDF Full-text (1590 KB) | HTML Full-text | XML Full-text
Abstract
Nowadays modified textiles, especially UV-protective, antibacterial and antimicrobial ones, have become the focus of great interest. In this study, several new UV absorbers, bis(indolyl)methane derivatives, were synthesized and grafted onto polyvinyl alcohol polymer (PVA). Their application properties on cotton-based textile materials were determined;
[...] Read more.
Nowadays modified textiles, especially UV-protective, antibacterial and antimicrobial ones, have become the focus of great interest. In this study, several new UV absorbers, bis(indolyl)methane derivatives, were synthesized and grafted onto polyvinyl alcohol polymer (PVA). Their application properties on cotton-based textile materials were determined; the UV protection factor values of the modified fabrics were measured (UPF); and the antibacterial features of the fabrics were tested. Full article
Figures

Open AccessArticle Synthesis, Spectroscopic, X-ray Diffraction and DFT Studies of Novel Benzimidazole Fused-1,4-Oxazepines
Molecules 2016, 21(6), 724; doi:10.3390/molecules21060724
Received: 16 April 2016 / Revised: 22 May 2016 / Accepted: 27 May 2016 / Published: 3 June 2016
PDF Full-text (4851 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[
[...] Read more.
A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[d]imidazol-1-yl)-butan-2-ol 9 and 10 3,3-dimethyl-N-phenyl-1,2,3,5-tetrahydrobenzo-[4,5]imidazo[2,1-c][1,4]oxazepin-5-amine using the B3LYP/6–31 G(d, p) method were found to agree well with their X-ray structures. The charge distributions at the different atomic sites were computed using the natural bond orbital (NBO) method. The regions of electrophilic and nucleophilic reactivity were shown using a molecular electrostatic potential (MEP) map. In addition, the frontier molecular orbitals of these compounds were discussed at the same level of theory. Nonlinear optical (NLO) properties have also been investigated by computational hyperpolarizability studies, and it was found that Compound 9 is the best candidate for NLO applications. Full article
Figures

Open AccessArticle Hydrazino-methoxy-1,3,5-triazine Derivatives’ Excellent Corrosion Organic Inhibitors of Steel in Acidic Chloride Solution
Molecules 2016, 21(6), 714; doi:10.3390/molecules21060714
Received: 29 April 2016 / Revised: 27 May 2016 / Accepted: 27 May 2016 / Published: 1 June 2016
Cited by 2 | PDF Full-text (2049 KB) | HTML Full-text | XML Full-text
Abstract
The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6-tridydrazino-1,3,5-triaizne (TH3) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy-1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at
[...] Read more.
The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6-tridydrazino-1,3,5-triaizne (TH3) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy-1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at a low concentration of 25 ppm (95%). The number of hydrazino groups play an important role in the corrosion inhibition, where the two hydrazine groups increased the electrostatic interactions between the protonated tested compounds, the negatively charged steel surface resulted from the adsorption of the chloride anions, and the presence of the methoxy group made the compound more reliable for formation of film protection on the surface of steel through the lone pair of oxygen atoms. Electrochemical Impedance Spectroscopy (EIS) measurements suggested that the corrosion process of steel in presence of the hydrazino-s-triazine derivatives (TH3, DMeHT and DHMeT) were being controlled by the charge transfer reaction. Polarization curves indicated that the examined TH3, DMeHT and DHMeT behaved as mixed type inhibitors. Full article
Figures

Open AccessArticle Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts
Molecules 2016, 21(6), 707; doi:10.3390/molecules21060707
Received: 12 April 2016 / Revised: 16 May 2016 / Accepted: 23 May 2016 / Published: 1 June 2016
Cited by 2 | PDF Full-text (3406 KB) | HTML Full-text | XML Full-text
Abstract
Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by
[...] Read more.
Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of 13C-CP/MAS and 15N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated. Full article
Figures

Open AccessArticle A Convenient Synthesis of 3,7′-Bisindole Derivatives
Molecules 2016, 21(5), 638; doi:10.3390/molecules21050638
Received: 15 March 2016 / Revised: 5 May 2016 / Accepted: 6 May 2016 / Published: 17 May 2016
PDF Full-text (1127 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient and convenient method to synthesize highly functionalized 3,7′-bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient,
[...] Read more.
An efficient and convenient method to synthesize highly functionalized 3,7′-bisindole derivatives has been developed via a Michael addition and cyclic condensation reaction of heterocyclic ketene aminals (HKAs) with 2-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione derivatives in ethanol-based solvents at room temperature. This strategy provides an efficient, environmentally friendly approach for easy access to various novel 3,7′-bisindole derivatives in moderate to good yields. Full article
Figures

Open AccessArticle Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines
Molecules 2016, 21(4), 514; doi:10.3390/molecules21040514
Received: 17 December 2015 / Revised: 8 April 2016 / Accepted: 13 April 2016 / Published: 21 April 2016
Cited by 1 | PDF Full-text (3370 KB) | HTML Full-text | XML Full-text
Abstract
Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH+ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a.
[...] Read more.
Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH+ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH+ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH+ subpopulation. Full article
Figures

Open AccessArticle A Green Ultrasound Synthesis, Characterization and Antibacterial Evaluation of 1,4-Disubstituted 1,2,3-Triazoles Tethering Bioactive Benzothiazole Nucleus
Molecules 2016, 21(4), 505; doi:10.3390/molecules21040505
Received: 11 March 2016 / Revised: 8 April 2016 / Accepted: 12 April 2016 / Published: 18 April 2016
Cited by 3 | PDF Full-text (3695 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides 5a–r via the 1,3-dipolar cycloaddition reaction between 2-azido-N-(benzo[d]thiazol-2-yl)acetamide derivatives 3a–c and different alkynes were performed in the presence and absence of ultrasound irradiation. The synthesis was carried out using t
[...] Read more.
The synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides 5a–r via the 1,3-dipolar cycloaddition reaction between 2-azido-N-(benzo[d]thiazol-2-yl)acetamide derivatives 3a–c and different alkynes were performed in the presence and absence of ultrasound irradiation. The synthesis was carried out using t-BuOH/H2O (1:1, v/v) as reaction solvents and CuSO4·5H2O/sodium ascorbate as the catalyst. The copper catalyst was implemented to provide the regioselective 1,4-disubstituted 1,2,3-triazoles 5a–r. Significant reductions in reaction times with comparably higher yields were observed when the reactions were carried out under ultrasound irradiation. The structures of the newly synthesized 1,2,3-triazoles were elucidated by IR, NMR, MS, and elemental analyses. They were also screened for their antimicrobial activity against three gram-positive (Streptococcus pneumonia, Bacillus subtilis, and Staphylococcus aureus), three gram-negative (Pseudomonas aeuroginosa, Escherichia coli, and Klebsiella pneumonia), and two fungal strains (Aspergillus fumigates and Candida albicans). Most of the tested compounds displayed promising antimicrobial activities at a Minimum Inhibition Concentration (MIC) of 4–16 μg/mL. Full article
Open AccessReview Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues
Molecules 2016, 21(4), 492; doi:10.3390/molecules21040492
Received: 22 February 2016 / Revised: 31 March 2016 / Accepted: 5 April 2016 / Published: 14 April 2016
Cited by 5 | PDF Full-text (16808 KB) | HTML Full-text | XML Full-text
Abstract
This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity,
[...] Read more.
This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds. Selected examples from the 2006 to 2015 literature are discussed. Full article
Figures

Open AccessArticle Investigation of the Pyridinium Ylide—Alkyne Cycloaddition as a Fluorogenic Coupling Reaction
Molecules 2016, 21(3), 332; doi:10.3390/molecules21030332
Received: 26 January 2016 / Revised: 3 March 2016 / Accepted: 4 March 2016 / Published: 10 March 2016
Cited by 1 | PDF Full-text (2260 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied,
[...] Read more.
The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied, and 11 indolizines, with three points of structural variation, were, thus, isolated and characterized. The highest yields were obtained when electron-withdrawing groups were present on both the pyridinium ylide, generated in situ from the corresponding pyridinium salt, and the alkyne (X, Z = ester, amide, CN, carbonyl, etc.). Electron-withdrawing substituents, lowering the acid dissociation constant (pKa) of the pyridinium salts, allow the cycloaddition to proceed at pH 7.5 in aqueous buffers at room temperature. Full article
Figures

Open AccessArticle Hydrazonoyl Chlorides as Precursors for Synthesis of Novel Bis-Pyrrole Derivatives
Molecules 2016, 21(3), 326; doi:10.3390/molecules21030326
Received: 30 January 2016 / Revised: 29 February 2016 / Accepted: 29 February 2016 / Published: 9 March 2016
PDF Full-text (3531 KB) | HTML Full-text | XML Full-text
Abstract
A convenient synthesis of some novel bis-pyrrole derivatives via hydrazonoyl halides is described. Antimicrobial evaluation of some selected examples of the synthesized products was carried out. The bis-pyrrole derivative having chloro substituents showed good activity against all of the used microbes. The molecular
[...] Read more.
A convenient synthesis of some novel bis-pyrrole derivatives via hydrazonoyl halides is described. Antimicrobial evaluation of some selected examples of the synthesized products was carried out. The bis-pyrrole derivative having chloro substituents showed good activity against all of the used microbes. The molecular docking of the bis-pyrrole derivatives was performed by the Molecular Operating Environment (MOE) program. Full article
Figures

Open AccessArticle Synthesis of Naphthalene-Based Push-Pull Molecules with a Heteroaromatic Electron Acceptor
Molecules 2016, 21(3), 267; doi:10.3390/molecules21030267
Received: 4 January 2016 / Revised: 18 February 2016 / Accepted: 22 February 2016 / Published: 2 March 2016
Cited by 1 | PDF Full-text (1573 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Naphthalene derivatives bearing electron-accepting and electron-donating groups at the 2,6-positions belong to the family of D-π-A push-pull dyes. It has been found that these compounds, e.g., 2-(1-(6-((2-(fluoro)ethyl)(methyl)amino)naphthalen-2-yl)ethylidene)malononitrile (FDDNP), show not only interesting optical properties, such as solvatochromism, but they have the potential to
[...] Read more.
Naphthalene derivatives bearing electron-accepting and electron-donating groups at the 2,6-positions belong to the family of D-π-A push-pull dyes. It has been found that these compounds, e.g., 2-(1-(6-((2-(fluoro)ethyl)(methyl)amino)naphthalen-2-yl)ethylidene)malononitrile (FDDNP), show not only interesting optical properties, such as solvatochromism, but they have the potential to label protein aggregates of different compositions formed in the brain of patients suffering from neurodegenerative diseases like Alzheimer’s (AD). In continuation of our research we set our goal to find new FDDNP analogs, which would inherit optical and binding properties but hopefully show better specificity for tau protein aggregates, which are characteristic for neurodegeneration caused by repetitive mild trauma. In this work we report on the synthesis of new FDDNP analogs in which the acceptor group has been formally replaced with an aromatic five- or six-membered heterocycle. The heterocyclic moiety was annealed to the central naphthalene ring either by classical ring closure reactions or by modern transition metal-catalyzed coupling reactions. The chemical characterization, NMR spectra, and UV/vis properties of all new compounds are reported. Full article
Open AccessArticle Conjugated Oligo-Aromatic Compounds Bearing a 3,4,5-Trimethoxy Moiety: Investigation of Their Antioxidant Activity Correlated with a DFT Study
Molecules 2016, 21(2), 224; doi:10.3390/molecules21020224
Received: 8 January 2016 / Revised: 4 February 2016 / Accepted: 5 February 2016 / Published: 17 February 2016
Cited by 4 | PDF Full-text (2349 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of heterocyclic compounds bearing the well-known free radical scavenging 3,4,5-trimethoxybenzyloxy group, was synthesized. The key compound 4-(3,4,5-trimethoxybenzyl-oxy)benzohydrazide was converted into thiosemicarbazide derivatives, which were subsequently cyclized with NaOH to provide 1,2,4-triazole derivatives. Alternative treatment of the acid hydrazide with carbon disulfide
[...] Read more.
A series of heterocyclic compounds bearing the well-known free radical scavenging 3,4,5-trimethoxybenzyloxy group, was synthesized. The key compound 4-(3,4,5-trimethoxybenzyl-oxy)benzohydrazide was converted into thiosemicarbazide derivatives, which were subsequently cyclized with NaOH to provide 1,2,4-triazole derivatives. Alternative treatment of the acid hydrazide with carbon disulfide in the presence of KOH led to the corresponding 1,3,4-oxadiazole and various alkylated derivatives. The newly synthesized compounds were purified and the structures of the products were elucidated and confirmed on the basis of their analytical and spectral data. Their antioxidant activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) assays. The thiosemicarbazide derivatives were highly active in both antioxidant assays with the lowest IC50 value for DPPH radical scavenging. Theoretical calculations based on density functional theory (DFT) were performed to understand the relative importance of NH, SH and CH hydrogens on the radical scavenging activities of these compounds. Full article
Figures

Open AccessArticle Synthesis of Some Novel 2-Amino-5-arylazothiazole Disperse Dyes for Dyeing Polyester Fabrics and Their Antimicrobial Activity
Molecules 2016, 21(1), 122; doi:10.3390/molecules21010122
Received: 20 December 2015 / Revised: 9 January 2016 / Accepted: 18 January 2016 / Published: 21 January 2016
Cited by 1 | PDF Full-text (1430 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present work describes the synthesis of a series of four novel biologically active 2-amino-5-arylazothiazole disperse dyes containing the sulfa drug nucleus. The structures of the synthesized thiazole derivatives are confirmed using UV-spectrophotometry, infrared and nuclear magnetic resonance techniques and elemental analysis. The
[...] Read more.
The present work describes the synthesis of a series of four novel biologically active 2-amino-5-arylazothiazole disperse dyes containing the sulfa drug nucleus. The structures of the synthesized thiazole derivatives are confirmed using UV-spectrophotometry, infrared and nuclear magnetic resonance techniques and elemental analysis. The synthesized dyes are applied to polyester fabrics as disperse dyes and their fastness properties to washing, perspiration, rubbing, sublimation, and light are evaluated. The synthesized compounds exhibit promising biological efficiency against selected Gram-positive and Gram-negative pathogenic bacteria as well as fungi. Full article

2015

Jump to: 2017, 2016

Open AccessArticle Syntheses of 4-Indolylquinoline Derivatives via Reductive Cyclization of Indolylnitrochalcone Derivatives by Fe/HCl
Molecules 2015, 20(12), 22499-22519; doi:10.3390/molecules201219862
Received: 23 November 2015 / Revised: 7 December 2015 / Accepted: 8 December 2015 / Published: 15 December 2015
PDF Full-text (17734 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An easy and efficient procedure for the synthesis of 4-indolylquinoline derivatives is described. This process involves two steps, the first of which is the Michael addition of indole to nitrochalcones promoted by sulfamic acid under solvent free conditions and the second step is
[...] Read more.
An easy and efficient procedure for the synthesis of 4-indolylquinoline derivatives is described. This process involves two steps, the first of which is the Michael addition of indole to nitrochalcones promoted by sulfamic acid under solvent free conditions and the second step is a reductive cyclization of the indolylnitrochalcone intermediates to 4-indolylquinoline derivatives by Fe/HCl in ethanol. In both steps, the reactions are clean and the yields of products are high. Full article
Open AccessArticle Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents
Molecules 2015, 20(12), 22069-22083; doi:10.3390/molecules201219827
Received: 19 October 2015 / Revised: 26 November 2015 / Accepted: 3 December 2015 / Published: 10 December 2015
Cited by 9 | PDF Full-text (4157 KB) | HTML Full-text | XML Full-text
Abstract
A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone
[...] Read more.
A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data. Full article
Figures

Open AccessArticle Eco-Friendly Synthesis of Some Thiosemicarbazones and Their Applications as Intermediates for 5-Arylazothiazole Disperse Dyes
Molecules 2015, 20(12), 21982-21991; doi:10.3390/molecules201219820
Received: 13 November 2015 / Revised: 30 November 2015 / Accepted: 3 December 2015 / Published: 9 December 2015
PDF Full-text (1088 KB) | HTML Full-text | XML Full-text
Abstract
The solid-solid reactions of thiosemicarbazide with 4-formylantipyrine, 2-acetylpyrrole and camphor were performed to afford the thiosemicarbazones 13 which underwent hetero-cyclization with phenacyl bromide to furnish the corresponding thiazole derivatives 46. The yields of the reactions are quantitative in
[...] Read more.
The solid-solid reactions of thiosemicarbazide with 4-formylantipyrine, 2-acetylpyrrole and camphor were performed to afford the thiosemicarbazones 13 which underwent hetero-cyclization with phenacyl bromide to furnish the corresponding thiazole derivatives 46. The yields of the reactions are quantitative in all cases and the products do not require further purification. A series of 5-arylazo-2-(substituted ylidene-hydrazinyl)-thiazole dyes 79 was then prepared by diazo coupling of thiazole derivatives 46 with several diazonium chlorides. The synthesized dyes were applied as disperse dyes for dyeing polyester fabric. The dyed fabrics exhibit good washing, perspiration, sublimation and light fastness properties, with little variation in their moderate to good rubbing fastness. Full article
Figures

Open AccessArticle Utility of 3-Acetyl-6-bromo-2H-chromen-2-one for the Synthesis of New Heterocycles as Potential Antiproliferative Agents
Molecules 2015, 20(12), 21826-21839; doi:10.3390/molecules201219803
Received: 27 August 2015 / Revised: 25 November 2015 / Accepted: 26 November 2015 / Published: 4 December 2015
Cited by 9 | PDF Full-text (900 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Coumarin derivatives containing pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyrimidine, 1,3,4-thiadiazoles and thiazoles were synthesized from 6-bromo-3-(3-(dimethylamino)acryloyl)-2H-chromen-2-one, methyl 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbodithioate, 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene) hydrazine carbothioamide and each of heterocyclic amine, hydrazonoyl chlorides and hydroximoyl
[...] Read more.
Coumarin derivatives containing pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyrimidine, 1,3,4-thiadiazoles and thiazoles were synthesized from 6-bromo-3-(3-(dimethylamino)acryloyl)-2H-chromen-2-one, methyl 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbodithioate, 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene) hydrazine carbothioamide and each of heterocyclic amine, hydrazonoyl chlorides and hydroximoyl chlorides. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Moreover, selected newly synthesized products were evaluated for their antitumor activity against a liver carcinoma cancer cell line (HEPG2-1). The results revealed that pyrazolo[1,5-a]pyrimidine 7c, thiazole 23g and 1,3,4-thiadiazole 18a (IC50 = 2.70 ± 0.28, 3.50 ± 0.23 and 4.90 ± 0.69 µM, respectively) have promising antitumor activity against liver carcinoma (HEPG2-1) while most of the tested compounds showed moderate activity. Full article
Figures

Open AccessArticle Synthesis and Antimicrobial Evaluation of a New Series of Heterocyclic Systems Bearing a Benzosuberone Scaffold
Molecules 2015, 20(11), 20434-20447; doi:10.3390/molecules201119701
Received: 11 September 2015 / Revised: 30 October 2015 / Accepted: 4 November 2015 / Published: 16 November 2015
Cited by 2 | PDF Full-text (1396 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives 1a,b as starting materials. Treatment of 1a,b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to
[...] Read more.
A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives 1a,b as starting materials. Treatment of 1a,b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to afford the thioamides 4a,b, which was reacted with methyl iodide to obtain methylated products 5a,b. Cyclocondensation of 4a,b with chloroacetone 6 and phenacyl chloride 7 gave the corresponding thiophene derivatives 9ac. Reaction of 4a,b with C-acetyl-N- arylhydrazonoyl chlorides 14a and 14b in boiling EtOH in the presence of triethylamine, afforded the corresponding 1,3,4-thiadiazoline derivatives 16ad. The thioamides 4a,b were reacted with C-ethoxycarbonyl-N-arylhydrazonoyl chlorides 18a,b which afforded 1,3,4-thiadiazoline derivatives 19ad. The benzosuberones 1a,b were treated with 3-mercaptopropanoic acid to give compounds 21a,b, which were cyclized to tricyclic thiopyran-4(5H)-one derivatives 22a,b. The latter compounds 22a,b were reacted with 3-mercaptopropanoic acid to give compounds 23a,b, which were cyclized tetracyclic ring systems 24a,b. Finally, compounds 24a,b were oxidized using hydrogen peroxide under reflux conditions to afford the oxidized form of the novel tetracyclic heterogeneous ring systems 25a,b. The newly synthesized compounds were screened for antimicrobial activities. The structures of new compounds were characterized by 1H-NMR, 13C-NMR, IR, and EI-MS. Full article
Open AccessArticle Direct Aminolysis of Ethoxycarbonylmethyl 1,4-Dihydropyridine-3-carboxylates
Molecules 2015, 20(11), 20341-20354; doi:10.3390/molecules201119697
Received: 24 September 2015 / Revised: 22 October 2015 / Accepted: 27 October 2015 / Published: 12 November 2015
Cited by 1 | PDF Full-text (1839 KB) | HTML Full-text | XML Full-text
Abstract
The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines
[...] Read more.
The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines as without it the reaction does not proceed at all. The aminolysis reaction proceeded regioselectively, as the alkyl ester conjugated with the 1,4-dihydropyridine cycle was not involved in the reaction. Screening of other N-containing bases, such as triethylamine (TEA), pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), imidazole, tetramethyl guanidine (TMG) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) as catalysts revealed no activity in the studied reaction. Full article
Figures

Open AccessArticle Synthesis of Novel β-Keto-Enol Derivatives Tethered Pyrazole, Pyridine and Furan as New Potential Antifungal and Anti-Breast Cancer Agents
Molecules 2015, 20(11), 20186-20194; doi:10.3390/molecules201119684
Received: 4 September 2015 / Revised: 30 October 2015 / Accepted: 2 November 2015 / Published: 10 November 2015
Cited by 8 | PDF Full-text (2634 KB) | HTML Full-text | XML Full-text
Abstract
Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a
[...] Read more.
Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241) human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO). Three of the synthesized compounds showed potent activity against fungal strains with IC50 values in the range of 0.055–0.092 µM. The results revealed that these compounds showed better IC50 values while compared with positive controls. Full article
Figures

Open AccessArticle Efficient Syntheses of 1,2,3-Triazoloamide Derivatives Using Solid- and Solution-Phase Synthetic Approaches
Molecules 2015, 20(11), 19984-20013; doi:10.3390/molecules201119673
Received: 16 September 2015 / Revised: 28 October 2015 / Accepted: 29 October 2015 / Published: 5 November 2015
Cited by 3 | PDF Full-text (3027 KB) | HTML Full-text | XML Full-text
Abstract
Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3-triazoloamide derivatives were developed. A secondary α-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The
[...] Read more.
Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3-triazoloamide derivatives were developed. A secondary α-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The synthetic routes rely on amide formation with secondary amines and chloro-acid chlorides; SN2 reaction with sodium azide; and the selective [3 + 2] Hüisgen cycloaddition with appropriate terminal alkynes. The target secondary and tertiary 1,2,3-triazoloamide derivatives were obtained with three-diversity points in excellent overall yields and purities using the reported solid- and solution-phase synthetic routes, respectively. Full article
Figures

Open AccessArticle Novel 2-Thioxanthine and Dipyrimidopyridine Derivatives: Synthesis and Antimicrobial Activity
Molecules 2015, 20(10), 19263-19276; doi:10.3390/molecules201019263
Received: 22 August 2015 / Revised: 3 October 2015 / Accepted: 12 October 2015 / Published: 22 October 2015
Cited by 2 | PDF Full-text (728 KB) | HTML Full-text | XML Full-text
Abstract
Several fused imidazolopyrimidines were synthesized starting from 6-amino-1-methyl-2-thiouracil (1) followed by nitrosation, reduction and condensation with different aromatic aldehydes to give Schiff’s base. The dehydrocyclization of Schiff’s bases using iodine/DMF gave Compounds 5ag. The methylation of 5a
[...] Read more.
Several fused imidazolopyrimidines were synthesized starting from 6-amino-1-methyl-2-thiouracil (1) followed by nitrosation, reduction and condensation with different aromatic aldehydes to give Schiff’s base. The dehydrocyclization of Schiff’s bases using iodine/DMF gave Compounds 5ag. The methylation of 5ag using a simple alkylating agent as dimethyl sulfate ((CH3)2SO4) gave either monoalkylated imidazolopyrimidine 6ag at room temperature or dialkylated derivatives 7ag on heating 6ag with ((CH3)2SO4). On the other hand, treatment of 1 with different aromatic aldehydes in absolute ethanol in the presence of conc. hydrochloric acid at room temperature and/or reflux with acetic acid afforded bis-5,5́-diuracylmethylene 8ae, which cyclized on heating with a mixture of acetic acid/HCl (1:1) to give 9ae. Compounds 9ae can be obtained directly by refluxing of Compound 1 with a mixture of acetic acid/HCl. The synthesized new compounds were screened for antimicrobial activity, and the MIC was measured. Full article
Figures

Open AccessArticle Synthesis of Some Novel Heterocyclic and Schiff Base Derivatives as Antimicrobial Agents
Molecules 2015, 20(10), 18201-18218; doi:10.3390/molecules201018201
Received: 5 September 2015 / Revised: 20 September 2015 / Accepted: 23 September 2015 / Published: 7 October 2015
Cited by 6 | PDF Full-text (864 KB) | HTML Full-text | XML Full-text
Abstract
Treatment of 2,3-diaryloxirane-2,3-dicarbonitriles 1ac with different nitrogen nucleophiles, e.g., hydrazine, methyl hydrazine, phenyl hydrazine, hydroxylamine, thiosemicarbazide, and/or 2-amino-5-phenyl-1,3,4-thiadiazole, afforded pyrazole, isoxazole, pyrrolotriazine, imidazolothiadiazole derivatives 25, respectively. Reacting pyrazoles 2ac with aromatic aldehydes and/or methyl glycinate produced
[...] Read more.
Treatment of 2,3-diaryloxirane-2,3-dicarbonitriles 1ac with different nitrogen nucleophiles, e.g., hydrazine, methyl hydrazine, phenyl hydrazine, hydroxylamine, thiosemicarbazide, and/or 2-amino-5-phenyl-1,3,4-thiadiazole, afforded pyrazole, isoxazole, pyrrolotriazine, imidazolothiadiazole derivatives 25, respectively. Reacting pyrazoles 2ac with aromatic aldehydes and/or methyl glycinate produced Schiff’s bases 7ad and pyrazolo[3,4-b]-pyrazinone derivative 8, respectively. Treating 7 with ammonium acetate and/or hydrazine hydrate, furnished the imidazolopyrazole and pyrazolotriazine derivatives 9 and 10, respectively. Reaction of 8 with chloroacetic acid and/or diethyl malonate gave tricyclic compound 11 and triketone 12, respectively. On the other hand, compound 1 was reacted with active methylene precursors, e.g., acetylacetone and/or cyclopentanone producing adducts 14a,b which upon fusion with ammonium acetate furnished the 3-pyridone derivatives 15a,b, respectively. Some of newly synthesized compounds were screened for activity against bacterial and fungal strains and most of the newly synthesized compounds showed high antimicrobial activities. The structures of the new compounds were elucidated using IR, 1H-NMR, 13C-NMR and mass spectroscopy. Full article
Open AccessReview Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine’s Tool Box
Molecules 2015, 20(9), 16852-16891; doi:10.3390/molecules200916852
Received: 19 June 2015 / Revised: 8 September 2015 / Accepted: 9 September 2015 / Published: 16 September 2015
Cited by 42 | PDF Full-text (1892 KB) | HTML Full-text | XML Full-text
Abstract
The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many
[...] Read more.
The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles. Full article
Open AccessArticle Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin
Molecules 2015, 20(9), 15643-15665; doi:10.3390/molecules200915643
Received: 6 July 2015 / Revised: 15 August 2015 / Accepted: 17 August 2015 / Published: 28 August 2015
Cited by 6 | PDF Full-text (1357 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (1H,
[...] Read more.
A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (1H, 13C, 19F and 15N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure–activity analysis allowed the establishment of a correlation between the presence/ absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[β-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1H-pyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms. Full article
Figures

Open AccessArticle Synthesis and Photophysical Properties of Polycarbo-Substituted Quinazolines Derived from the 2-Aryl-4-chloro-6-iodoquinazolines
Molecules 2015, 20(8), 14656-14683; doi:10.3390/molecules200814656
Received: 3 July 2015 / Revised: 3 August 2015 / Accepted: 7 August 2015 / Published: 13 August 2015
Cited by 2 | PDF Full-text (2341 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The reactivity of the 2-aryl-4-chloro-6-iodoquinazolines towards palladium catalyzed sequential (Sonogashira/Suzuki-Miyaura) and one-pot two-step cross-coupling (bis-Sonogashira, and successive Sonogashira/Stille) reactions to afford novel unsymmetrical polycarbo-substituted quinazolines has been evaluated. In contrast to the chloro-bromo substituted quinazolines in which selectivity has been previously found to
[...] Read more.
The reactivity of the 2-aryl-4-chloro-6-iodoquinazolines towards palladium catalyzed sequential (Sonogashira/Suzuki-Miyaura) and one-pot two-step cross-coupling (bis-Sonogashira, and successive Sonogashira/Stille) reactions to afford novel unsymmetrical polycarbo-substituted quinazolines has been evaluated. In contrast to the chloro-bromo substituted quinazolines in which selectivity has been previously found to generally favor substitution at the more activated C(4)-Cl bond over the weaker Csp2-Br bond, substitution in the case of the chloro-iodo derivatives favors cross-coupling through the intrinsically more reactive Csp2-I bond. The electronic absorption and emission properties of the prepared 2,3-diaryl-6-(phenylethynyl)quinazolines were studied in solvents of different polarity (dichloromethane, toluene, DMF, methanol) and CH2Cl2-TFA mixture using UV-Vis and emission spectroscopic techniques complemented with density functional theory method to establish the effect of substituents on intramolecular charge transfer properties. Full article
Figures

Open AccessReview Synthesis and Consecutive Reactions of α-Azido Ketones: A Review
Molecules 2015, 20(8), 14699-14745; doi:10.3390/molecules200814699
Received: 20 April 2015 / Revised: 29 May 2015 / Accepted: 3 June 2015 / Published: 13 August 2015
Cited by 3 | PDF Full-text (1930 KB) | HTML Full-text | XML Full-text
Abstract
This review paper covers the major synthetic approaches attempted towards the synthesis of α-azido ketones, as well as the synthetic applications/consecutive reactions of α-azido ketones. Full article
Figures

Open AccessReview Recent Developments and Biological Activities of N-Substituted Carbazole Derivatives: A Review
Molecules 2015, 20(8), 13496-13517; doi:10.3390/molecules200813496
Received: 22 March 2015 / Revised: 9 June 2015 / Accepted: 24 June 2015 / Published: 23 July 2015
Cited by 16 | PDF Full-text (757 KB) | HTML Full-text | XML Full-text
Abstract
Carbazoles represent an important class of heterocycles. These have been reported to exhibit diverse biological activities such as antimicrobial, antitumor, antiepileptic, antihistaminic, antioxidative, anti-inflammatory, antidiarrhoeal, analgesic, neuroprotective and pancreatic lipase inhibition properties. A series of carbazole derivatives such as N-substituted carbazoles, benzocarbazoles,
[...] Read more.
Carbazoles represent an important class of heterocycles. These have been reported to exhibit diverse biological activities such as antimicrobial, antitumor, antiepileptic, antihistaminic, antioxidative, anti-inflammatory, antidiarrhoeal, analgesic, neuroprotective and pancreatic lipase inhibition properties. A series of carbazole derivatives such as N-substituted carbazoles, benzocarbazoles, furocarbazoles, pyrrolocarbazoles, indolocarbazoles, imidazocarbazoles, etc. have been synthesized. The N-substituted derivatives have gained the attention of researchers due to their therapeutic potential against neurological disorders and cell proliferation. Herein an attempt is made to review the medicinal importance of recently synthesized N-substituted carbazoles. Full article
Open AccessArticle Heterocycles 38. Biocatalytic Synthesis of New Heterocyclic Mannich Bases and Derivatives
Molecules 2015, 20(7), 12300-12313; doi:10.3390/molecules200712300
Received: 2 June 2015 / Revised: 1 July 2015 / Accepted: 2 July 2015 / Published: 6 July 2015
PDF Full-text (842 KB) | HTML Full-text | XML Full-text
Abstract
This paper describes the biocatalytic synthesis of new Mannich bases containing various heterocyclic rings (thiazole, furane, thiophene, pyridine) by applying the lipase catalyzed trimolecular condensation of the corresponding heterocyclic aldehydes with acetone and primary aromatic amines, in mild and eco-friendly reaction conditions. The
[...] Read more.
This paper describes the biocatalytic synthesis of new Mannich bases containing various heterocyclic rings (thiazole, furane, thiophene, pyridine) by applying the lipase catalyzed trimolecular condensation of the corresponding heterocyclic aldehydes with acetone and primary aromatic amines, in mild and eco-friendly reaction conditions. The obtained Mannich bases were acylated to their corresponding N-acetyl derivatives. All compounds were characterized by 1H-NMR, 13C-NMR and MS spectrometry. Full article
Figures

Open AccessArticle Uses of 3-(2-Bromoacetyl)-2H-chromen-2-one in the Synthesis of Heterocyclic Compounds Incorporating Coumarin: Synthesis, Characterization and Cytotoxicity
Molecules 2015, 20(6), 11535-11553; doi:10.3390/molecules200611535
Received: 1 June 2015 / Revised: 17 June 2015 / Accepted: 18 June 2015 / Published: 23 June 2015
Cited by 3 | PDF Full-text (1313 KB) | HTML Full-text | XML Full-text
Abstract
In this work, 3-bromoacetylcoumarin was used as the key starting material for the synthesis of pyran, pyridine, thiophene, thiazole and pyrazole derivatives through its reaction with different reagents. The structures of the newly synthesized compounds were confirmed on the basis of their spectral
[...] Read more.
In this work, 3-bromoacetylcoumarin was used as the key starting material for the synthesis of pyran, pyridine, thiophene, thiazole and pyrazole derivatives through its reaction with different reagents. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All of the synthesized compounds were screened for their in vitro anticancer activity against six human cancer cell lines, namely: human gastric cancer (NUGC), human colon cancer (DLD1), human liver cancer (HA22T and HEPG2), nasopharyngeal carcinoma (HONE1), human breast cancer (MCF) and normal fibroblast cells (WI38). The IC50 values (the sample concentration that produces 50% reduction in cell growth) in nanomolars (nM)) showed most of the compounds exhibited significant cytotoxic effect. Among these derivatives, compound 6d showed almost equipotent cytotoxic activity against NUGC (IC50 = 29 nM) compared to the standard CHS 828 (IC50 = 25 nM). Full article
Figures

Open AccessArticle Synthesis, Characterization, Antimicrobial Screening and Free-Radical Scavenging Activity of Some Novel Substituted Pyrazoles
Molecules 2015, 20(6), 10468-10486; doi:10.3390/molecules200610468
Received: 26 April 2015 / Revised: 1 June 2015 / Accepted: 1 June 2015 / Published: 8 June 2015
Cited by 5 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text
Abstract
The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same
[...] Read more.
The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1H-NMR, 13C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively. Full article
Figures

Open AccessArticle Synthesis, In-Vitro Antibacterial, Antifungal, and Molecular Modeling of Potent Anti-Microbial Agents with a Combined Pyrazole and Thiophene Pharmacophore
Molecules 2015, 20(5), 8712-8729; doi:10.3390/molecules20058712
Received: 5 April 2015 / Accepted: 11 May 2015 / Published: 14 May 2015
Cited by 5 | PDF Full-text (1867 KB) | HTML Full-text | XML Full-text
Abstract
Ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (2) and there derivatives 3ac, 4, 6ac and 9af were synthesized. The structure of compound 2 was deduced by 1H-NMR, 13C-NMR, FT-IR, MS, microanalysis, and single-crystal X-ray crystallography. The
[...] Read more.
Ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (2) and there derivatives 3ac, 4, 6ac and 9af were synthesized. The structure of compound 2 was deduced by 1H-NMR, 13C-NMR, FT-IR, MS, microanalysis, and single-crystal X-ray crystallography. The compound crystallized in the monoclinic system, with space group P21/c and cell coordinates a = 8.5752(16) Å, b = 21.046(4) Å, c = 8.2941(12) Å, β = 101.131(6)°, V = 1468.7(4) Å3, and Z = 4. Compounds 2, 3ac, 4, 5ac and 9af were subjected into in vitro antimicrobial activity tests. Compounds 3a and 3c were more potent than standard drug amphotericin B, showing MIC values of 23.8 ± 0.42 and 24.3 ± 0.68, respectively, against Aspergillus fumigatus while the standard drug MIC was 23.7 ± 0.1. Compound 3c was also more potent (MIC 24.8 ± 0.64) than the standard drug amphotericin B (MIC 19.7 ± 0.2) against Syncephalastrum racemosum. Compounds 4 and 9f also showed promising anti-microbial activity. Molecular modeling was performed for the most active compounds. Full article
Figures

Open AccessArticle Synthesis, Molecular Structure and Spectroscopic Investigations of Novel Fluorinated Spiro Heterocycles
Molecules 2015, 20(5), 8223-8241; doi:10.3390/molecules20058223
Received: 7 April 2015 / Revised: 29 April 2015 / Accepted: 29 April 2015 / Published: 7 May 2015
Cited by 5 | PDF Full-text (2614 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This paper describes an efficient and regioselective method for the synthesis of novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl- 2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4-(trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were characterized
[...] Read more.
This paper describes an efficient and regioselective method for the synthesis of novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl- 2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4-(trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were characterized by single-crystal X-ray diffraction, FT-IR and NMR techniques. The optimized geometrical parameters, infrared vibrational frequencies and NMR chemical shifts of the studied compounds have also been calculated using the density functional theory (DFT) method, using Becke-3-Lee-Yang-Parr functional and the 6-311G(d,p) basis set. There is good agreement between the experimentally determined structural parameters, vibrational frequencies and NMR chemical shifts of the studied compounds and those predicted theoretically. The calculated natural atomic charges using NBO method showed higher polarity of 3a compared to 3b.The calculated electronic spectra are also discussed based on the TD-DFT calculations. Full article
Figures

Open AccessArticle Synthesis, Crystal Structures and Spectroscopic Properties of Triazine-Based Hydrazone Derivatives; A Comparative Experimental-Theoretical Study
Molecules 2015, 20(4), 5851-5874; doi:10.3390/molecules20045851
Received: 14 February 2015 / Revised: 18 March 2015 / Accepted: 23 March 2015 / Published: 3 April 2015
Cited by 21 | PDF Full-text (2007 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report here a comparative theoretical and experimental study of four triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process from commercially available benzil and thiosemicarbazide. The structures of all compounds were determined by using the UV-Vis., FT-IR, NMR (
[...] Read more.
We report here a comparative theoretical and experimental study of four triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process from commercially available benzil and thiosemicarbazide. The structures of all compounds were determined by using the UV-Vis., FT-IR, NMR (1H and 13C) spectroscopic techniques and finally confirmed unequivocally by single crystal X-ray diffraction analysis. Experimental geometric parameters and spectroscopic properties of the triazine based hydrazones are compared with those obtained from density functional theory (DFT) studies. The model developed here comprises of geometry optimization at B3LYP/6-31G (d, p) level of DFT. Optimized geometric parameters of all four compounds showed excellent correlations with the results obtained from X-ray diffraction studies. The vibrational spectra show nice correlations with the experimental IR spectra. Moreover, the simulated absorption spectra also agree well with experimental results (within 10–20 nm). The molecular electrostatic potential (MEP) mapped over the entire stabilized geometries of the compounds indicated their chemical reactivates. Furthermore, frontier molecular orbital (electronic properties) and first hyperpolarizability (nonlinear optical response) were also computed at the B3LYP/6-31G (d, p) level of theory. Full article
Figures

Back to Top