Special Issue "Heterocycles"

A special issue of Molbank (ISSN 1422-8599). This special issue belongs to the section "Organic Synthesis".

Deadline for manuscript submissions: closed (31 December 2017).

Special Issue Editor

Guest Editor
Prof. Dr. Richard A. Bunce Website E-Mail
Oklahoma State University, Department of Chemistry, Stillwater, Oklahoma, United States
Interests: new synthetic methodology; heterocycles; antibacterial agents; anticancer agents; medicinal chemistry

Special Issue Information

Dear Colleagues,

Heterocycles are ubiquitous building blocks in natural and unnatural medicinal compounds and functional materials. The focus of this Special Issue is to present short papers describing novel synthetic approaches to heterocyclic structures of value in these areas. Efficient procedures to access ring systems containing one or more heteroatoms (particularly, N, O and S, as well as others) are welcome. Contributions should be written as single-compound preparations and should target new compounds of high value. Previously-described structures will only be considered if they have proven value and if a significant improvement has been made in the synthetic approach. Sufficient experimental details should be included to facilitate other researchers in accessing each compound and characterization data should be included.

Prof. Dr. Richard A. Bunce
Guest Editor

Manuscript Submission Information

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Keywords

  • heterocycle synthesis
  • novel synthetic strategies
  • natural and unnatural medicinal compounds
  • functional materials chemistry

Published Papers (13 papers)

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Research

Open AccessCommunication
2-[2-Methyl-5-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-pyrrol-3-yl]-2-oxo-N-(pyridin-4-yl) acetamide
Molbank 2018, 2018(3), 1002; https://doi.org/10.3390/M1002 - 28 Jun 2018
Cited by 1
Abstract
We synthesized 2-[2-methyl-5-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-pyrrol-3-yl]-2-oxo-N-(pyridin-4-yl) acetamide 4 as a novel compound derived from the indibulin and combretastatin scaffolds, which are known anti-mitotic agents, using a multistep reaction. We tested its cytotoxic activity against three breast cancer cell lines, namely, MCF-7, T47-D, [...] Read more.
We synthesized 2-[2-methyl-5-phenyl-1-(3,4,5-trimethoxyphenyl)-1H-pyrrol-3-yl]-2-oxo-N-(pyridin-4-yl) acetamide 4 as a novel compound derived from the indibulin and combretastatin scaffolds, which are known anti-mitotic agents, using a multistep reaction. We tested its cytotoxic activity against three breast cancer cell lines, namely, MCF-7, T47-D, and MDA-MB 231 as well as normal cell line NIH-3T3, by 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The biological activity results showed good cytotoxicity on cancerous cell lines (IC50 value 27.7–39.2 µM) and low toxicity on normal cell line (NIH-3T3, IC50 value > 100 µM). Full article
(This article belongs to the Special Issue Heterocycles)
Open AccessCommunication
1-[1-(4-Chlorobenzenesulfonyl)-1H-indole-3-yl]-3-[4-(pyridin-2-yl)piperazin-1-yl]propan-1-one
Molbank 2018, 2018(2), M991; https://doi.org/10.3390/M991 - 18 Apr 2018
Cited by 1
Abstract
The title compound was prepared by an aza-Michael addition reaction between 1-[1-(4-chlorobenzenesulfonyl)-1H-indole-3-yl]prop-2-en-1-one and 2-piridylpiperazine catalyzed by SiO2. The structural identity of the title compound was proven by elemental analysis and spectroscopic methods (IR, NMR). The compound was assayed in [...] Read more.
The title compound was prepared by an aza-Michael addition reaction between 1-[1-(4-chlorobenzenesulfonyl)-1H-indole-3-yl]prop-2-en-1-one and 2-piridylpiperazine catalyzed by SiO2. The structural identity of the title compound was proven by elemental analysis and spectroscopic methods (IR, NMR). The compound was assayed in a binding assay at the 5-HT6 receptor, showing poor affinity. Full article
(This article belongs to the Special Issue Heterocycles)
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Open AccessShort Note
(Z)-4-[2-(3,4-Difluorophenyl)hydrazono]-3-methyl-1H-pyrazol-5(4H)-one
Molbank 2018, 2018(2), M989; https://doi.org/10.3390/M989 - 31 Mar 2018
Abstract
The title compound (Z)-4-[2-(3,4-difluorophenyl)hydrazono]-3-methyl-1H-pyrazol-5(4H)-one 4 was synthesized by the reaction of ethyl 2-[2-(3,4-difluorophenyl)hydrazono]-3-oxobutanoate 3 with hydrazine hydrate. The diazotization of 3,4-difluoroaniline, followed by the treatment with ethyl acetoacetate, afforded intermediate 3. The synthesized compound 4 was [...] Read more.
The title compound (Z)-4-[2-(3,4-difluorophenyl)hydrazono]-3-methyl-1H-pyrazol-5(4H)-one 4 was synthesized by the reaction of ethyl 2-[2-(3,4-difluorophenyl)hydrazono]-3-oxobutanoate 3 with hydrazine hydrate. The diazotization of 3,4-difluoroaniline, followed by the treatment with ethyl acetoacetate, afforded intermediate 3. The synthesized compound 4 was characterized by FTIR, 1H-NMR, 13C-NMR and LCMS, and it showed synergistic anti-inflammatory, antiproliferative and antibacterial activities. Full article
(This article belongs to the Special Issue Heterocycles)
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Open AccessShort Note
1,3-Bis{[(E)-(9-ethyl-9H-carbazol-3-yl)methylene]amino}propan-2-ol
Molbank 2018, 2018(1), M986; https://doi.org/10.3390/M986 - 07 Mar 2018
Abstract
Condensation of 1,3-diaminopropan-2-ol with 9-ethyl-9H-carbazole-3-carbaldehyde in absolute ethanol under stirring condition resulted in the formation of 1,3-bis{[(E)-(9-ethyl-9H-carbazol-3-yl)methylidene]amino}propan-2-ol within 0.5 in an excellent yield. The structure of the desired Schiff base was physically analyzed via CHN-elemental analysis, TOF-MS, [...] Read more.
Condensation of 1,3-diaminopropan-2-ol with 9-ethyl-9H-carbazole-3-carbaldehyde in absolute ethanol under stirring condition resulted in the formation of 1,3-bis{[(E)-(9-ethyl-9H-carbazol-3-yl)methylidene]amino}propan-2-ol within 0.5 in an excellent yield. The structure of the desired Schiff base was physically analyzed via CHN-elemental analysis, TOF-MS, UV-vis, FT-IR, and 1H & 13C-NMR. Computational studies of the structure were performed at the DFT/B3LYP/6-311++G(d) level of theory. Molecular electrostatic potential (MEP), Mulliken charge, IR-B3LYP, and structure optimization were performed. Full article
(This article belongs to the Special Issue Heterocycles)
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Open AccessCommunication
N-Vinylation of Imidazole and Benzimidazole with a Paramagnetic Vinyl Bromide
Molbank 2018, 2018(1), M980; https://doi.org/10.3390/M980 - 01 Feb 2018
Cited by 1
Abstract
An N-vinylation of imidazole and benzimidazole with a paramagnetic vinyl bromide was investigated. Among the tested procedures, Pd-catalyzed reaction was the most powerful one. The N-vinylation of 2-aminobenzimidazole with a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde offered 1,1,3,3-tetramethyl-1H-benzimidazo[1,2-a]pyrrolo[3,4-e [...] Read more.
An N-vinylation of imidazole and benzimidazole with a paramagnetic vinyl bromide was investigated. Among the tested procedures, Pd-catalyzed reaction was the most powerful one. The N-vinylation of 2-aminobenzimidazole with a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde offered 1,1,3,3-tetramethyl-1H-benzimidazo[1,2-a]pyrrolo[3,4-e]pyrimidin-2(3H)-yloxyl radical and the corresponding non-cyclized Schiff base. The reaction of a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde with imidazole gave β-imidazo-α,β-unsaturated pyrroline nitroxide aldehyde, which was reduced to the alcohol and converted to an unstable allyl chloride. Full article
(This article belongs to the Special Issue Heterocycles)
Open AccessCommunication
N-(4-Bromobenzyl)-2-(5,6-dimethyl-1H-benzo[d]imid-azol-2-yl)benzeneamine
Molbank 2018, 2018(1), M979; https://doi.org/10.3390/M979 - 30 Jan 2018
Cited by 1
Abstract
N-(4-Bromobenzyl)-2-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)benzeneamine was obtained by condensation of N-(4-bromobenzyl)-3,1-benzoxazine-2,4-dione (N-(4-bromobenzyl)isatoic anhydride) with 4,5-dimethyl-1,2-phenylenediamine in refluxing acetic acid. This is a rare example of condensation of N-substituted 3,1-benzoxazine-2,4-dione with 1,2-phenylenediamine, which resulted in the formation of a [...] Read more.
N-(4-Bromobenzyl)-2-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)benzeneamine was obtained by condensation of N-(4-bromobenzyl)-3,1-benzoxazine-2,4-dione (N-(4-bromobenzyl)isatoic anhydride) with 4,5-dimethyl-1,2-phenylenediamine in refluxing acetic acid. This is a rare example of condensation of N-substituted 3,1-benzoxazine-2,4-dione with 1,2-phenylenediamine, which resulted in the formation of a benzimidazole derivative with a moderate yield. Crystallographic studies and initial biological screening were performed for the obtained product. Full article
(This article belongs to the Special Issue Heterocycles)
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Open AccessShort Note
5-Methyl-3,8-di-(2-amino-4-bromophenyl)-4,9-dioxa-1,2,6,7-tetraaza-5λ5-phosphaspiro[4.4]nona-2,7-diene
Molbank 2018, 2018(1), M978; https://doi.org/10.3390/M978 - 30 Jan 2018
Abstract
5-Methyl-3,8-di-(2-amino-4-bromophenyl)-4,9-dioxa-1,2,6,7-tetraaza-5λ5-phosphaspiro[4.4]nona-2,7-diene was obtained by condensation of 2-amino-5-bromobenzohydrazide and methylphosphonyl dichloride in the presence of triethylamine. An initial biological screening was performed for the resulting product. The synthesized compound showed relatively strong cytotoxic activity, which was, however, similar for cancer and non-cancer [...] Read more.
5-Methyl-3,8-di-(2-amino-4-bromophenyl)-4,9-dioxa-1,2,6,7-tetraaza-5λ5-phosphaspiro[4.4]nona-2,7-diene was obtained by condensation of 2-amino-5-bromobenzohydrazide and methylphosphonyl dichloride in the presence of triethylamine. An initial biological screening was performed for the resulting product. The synthesized compound showed relatively strong cytotoxic activity, which was, however, similar for cancer and non-cancer cell lines. Full article
(This article belongs to the Special Issue Heterocycles)
Open AccessCommunication
Straightforward Synthesis of N-Methyl-4-(pin)B-2(3H)-benzothiazol-2-one: A Promising Cross-Coupling Reagent
Molbank 2018, 2018(1), M976; https://doi.org/10.3390/M976 - 23 Jan 2018
Cited by 1
Abstract
Cyclo-condensation of N-methyl-2-bromoaniline with chlorocarbonylsulfenyl chloride (CCSC) promoted by PhNMe2 and AlCl3, afforded N-methyl-2-bromo-2(3H)-benzothiazol-2-one in good yield. Miyaura–Ishiyama cross-coupling of this brominated 2(3H)-benzothiazol-2-one with bis(pinacolato)diborone [(pin)2B2] produced a novel N [...] Read more.
Cyclo-condensation of N-methyl-2-bromoaniline with chlorocarbonylsulfenyl chloride (CCSC) promoted by PhNMe2 and AlCl3, afforded N-methyl-2-bromo-2(3H)-benzothiazol-2-one in good yield. Miyaura–Ishiyama cross-coupling of this brominated 2(3H)-benzothiazol-2-one with bis(pinacolato)diborone [(pin)2B2] produced a novel N-methyl-4-(pin)B-2(3H)-benzothiazol-2-one (3) using (pin)2B2 in the presence of the PdCl2(PPh3)2 catalyst. The obtained 4-(pin)B compound is regarded as a new entry for the library of Suzuki–Miyaura cross-coupling reactions. Full article
(This article belongs to the Special Issue Heterocycles)
Open AccessShort Note
5-Amino-3-methyl-1,2,4-thiadiazole
Molbank 2018, 2018(1), M977; https://doi.org/10.3390/M977 - 21 Jan 2018
Abstract
An improved procedure for isolation of 5-amino-3-methyl-1,2,4-thiadiazole in pure form on a multi-gram scale without chromatography is reported. Its 1H and 13C-NMR and IR data are presented and previously published erroneous data corrected. The molecular structure is confirmed by X-ray diffraction [...] Read more.
An improved procedure for isolation of 5-amino-3-methyl-1,2,4-thiadiazole in pure form on a multi-gram scale without chromatography is reported. Its 1H and 13C-NMR and IR data are presented and previously published erroneous data corrected. The molecular structure is confirmed by X-ray diffraction which shows layers consisting of an elaborate two-dimensional hydrogen bonded network of molecules. Full article
(This article belongs to the Special Issue Heterocycles)
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Open AccessCommunication
3-[2-(Oxiran-2-yl)ethyl]-1-{4-[(2-oxiran-2-yl)ethoxy]benzyl}imidazolium bis(Trifluoromethane)sulfonimide
Molbank 2018, 2018(1), M974; https://doi.org/10.3390/M974 - 13 Jan 2018
Abstract
The synthesis of 3-[2-(oxiran-2-yl)ethyl]-1-{4-[(2-oxiran-2-yl)ethoxy]benzyl}imidazolium bis(trifluoromethane)sulfonimide was achieved in seven steps with an overall yield of 63%. This ionic liquid monomer is based on an imidazolium core containing a phenoxy moiety and aliphatic chains with a reactive epoxide at both ends. This imidazolium was [...] Read more.
The synthesis of 3-[2-(oxiran-2-yl)ethyl]-1-{4-[(2-oxiran-2-yl)ethoxy]benzyl}imidazolium bis(trifluoromethane)sulfonimide was achieved in seven steps with an overall yield of 63%. This ionic liquid monomer is based on an imidazolium core containing a phenoxy moiety and aliphatic chains with a reactive epoxide at both ends. This imidazolium was obtained by an efficient, reproducible, and scalable synthesis from inexpensive reagents. In the last step, a powerful oxidative agent was successfully used to generate two epoxy functions with only acetone as a byproduct. The monomer structure and intermediates were analyzed by NMR experiments, infrared, and mass spectra. In addition, the thermal properties of the diepoxide were evaluated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Full article
(This article belongs to the Special Issue Heterocycles)
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Open AccessFeature PaperShort Note
1,3-Bis[(E)-(3-bromobenzylidene)amino]propan-2-ol
Molbank 2017, 2017(4), M971; https://doi.org/10.3390/M971 - 19 Dec 2017
Cited by 2
Abstract
1,3-Bis[(E)-(3-bromobenzylidene)amino]propan-2-ol Schiff base was synthesized in an acceptable yield by condensation of 3-bromobenzaldehyde with 1,3-diaminopropan-2-ol in methanol. The structure of the desired Schiff base compound was spectroscopically analyzed by EI-MS, CHN-elemental analysis, FT-IR, UV-visible, and 1H and 13C-NMR. The [...] Read more.
1,3-Bis[(E)-(3-bromobenzylidene)amino]propan-2-ol Schiff base was synthesized in an acceptable yield by condensation of 3-bromobenzaldehyde with 1,3-diaminopropan-2-ol in methanol. The structure of the desired Schiff base compound was spectroscopically analyzed by EI-MS, CHN-elemental analysis, FT-IR, UV-visible, and 1H and 13C-NMR. The structure was also computed by DFT-optimization, MEP, Mulliken, NPA, IR- B3LYP/6-311++G(d), and SCF-TD-DFT. Full article
(This article belongs to the Special Issue Heterocycles)
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Open AccessShort Note
4-Phenethylthio-2-phenylpyrazolo[1,5-a][1,3,5]triazin-7(6H)-one
Molbank 2017, 2017(4), M970; https://doi.org/10.3390/M970 - 15 Dec 2017
Cited by 2
Abstract
Exploring the pharmacologically important pyrazolo[1,5-a][1,3,5]triazin-7(6H)-one scaffold for the construction of new bioactive compounds, we developed a synthesis of 4-phenethylthio-2-phenylpyrazolo[1,5-a][1,3,5]triazin-7(6H)-one (4) via S-alkylation of 2-phenyl-4-thioxopyrazolo[1,5-a][1,3,5]triazine-7(6H)-one (3), prepared [...] Read more.
Exploring the pharmacologically important pyrazolo[1,5-a][1,3,5]triazin-7(6H)-one scaffold for the construction of new bioactive compounds, we developed a synthesis of 4-phenethylthio-2-phenylpyrazolo[1,5-a][1,3,5]triazin-7(6H)-one (4) via S-alkylation of 2-phenyl-4-thioxopyrazolo[1,5-a][1,3,5]triazine-7(6H)-one (3), prepared by the double ring closure of pyrazole and triazine rings upon the treatment of 1-cyanoacetyl-4-benzoylthiosemicarbazide (2) with alkali. The antiproliferative activity of 4 against human lung cancer (A549) and human breast cancer (MDA-MB231) cell lines was investigated. Compound 4 was found to be more active against lung cancer cells than breast cancer cells. Full article
(This article belongs to the Special Issue Heterocycles)
Open AccessCommunication
(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione—Synthesis and Crystallographic Studies
Molbank 2017, 2017(4), M964; https://doi.org/10.3390/M964 - 27 Oct 2017
Cited by 3
Abstract
(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione was obtained in a three-step, one-pot synthesis, starting from optically pure (S)-2-piperazine carboxylic acid dihydrochloride. Selective acylation of the β-nitrogen atom followed by condensation with isatoic anhydride and cyclization [...] Read more.
(S)-2-(4-Chlorobenzoyl)-1,2,3,4-tetrahydrobenzo[e]pyrazino[1,2-a][1,4]diazepine-6,12(11H,12aH)-dione was obtained in a three-step, one-pot synthesis, starting from optically pure (S)-2-piperazine carboxylic acid dihydrochloride. Selective acylation of the β-nitrogen atom followed by condensation with isatoic anhydride and cyclization with HATU/DIPEA to a seven-member benzodiazepine ring, led to the tricyclic benzodiazepine derivative. Crystallographic studies and initial biological screening were performed for the title compound. Full article
(This article belongs to the Special Issue Heterocycles)
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