Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines

The reaction of pyrazolo[1,5-a]pyrazine-4(5H)ones with phosphorus tribromoxide in boiling benzene yielded 4-bromopyrazolo[1,5-a]pyrazines, and the thionation with phosphorus pentasulfide in pyridine at 90 °C led to pyrazolo[1,5-a]pyrazine-4(5H)thiones. The synthesized bromine derivatives are electro...

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Дата:2019
Автори: Hrynyshyn, Yevhenii, Musiichuk, Hanna, Komarovska-Porokhnyavets, Olena, Is’kiv, Oksana, Moskalenko, Nataliia, Stasevych, Maryna, Tsyzoryk, Nazar, Vovk, Mykhailo
Формат: Стаття
Мова:English
Опубліковано: V.I.Vernadsky Institute of General and Inorganic Chemistry 2019
Онлайн доступ:https://ucj.org.ua/index.php/journal/article/view/22
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Назва журналу:Ukrainian Chemistry Journal

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Ukrainian Chemistry Journal
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spelling oai:ojs2.1444248.nisspano.web.hosting-test.net:article-222019-04-19T09:19:07Z Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines Hrynyshyn, Yevhenii Musiichuk, Hanna Komarovska-Porokhnyavets, Olena Is’kiv, Oksana Moskalenko, Nataliia Stasevych, Maryna Tsyzoryk, Nazar Vovk, Mykhailo 4-bromopyrazolo[1,5-a]pyrazines, pyrazolo[1,5-a]pyrazin-4(5H) thiones, thiophenoles, functionalized bromoalkanes, 4-aryl(alkyl)thio derivatives of pyrazolo[1,5-a]pyrazines, antibacterial and antifungal activity. The reaction of pyrazolo[1,5-a]pyrazine-4(5H)ones with phosphorus tribromoxide in boiling benzene yielded 4-bromopyrazolo[1,5-a]pyrazines, and the thionation with phosphorus pentasulfide in pyridine at 90 °C led to pyrazolo[1,5-a]pyrazine-4(5H)thiones. The synthesized bromine derivatives are electrophilic, and thiones are nucleophilic substrates. Their subsequent structural modification in the first case was carried out by interaction with thiophenols, and in the second case was conducted with functional halogenoalkanes. It was shown that bromides react with substituted thiophenols in dimethylformamide in the presence of potassium carbonate at 90 °C to form 4-arylthiopyrazolo[1,5-a]pyrazines with yields of 65–83 %. 4-S-methyl-functionalized derivatives of pyrazole[1,5-a]pyrazines with yields of 60–78 % were easily obtained by the alkylation of pyrazole[1,5-a]pyrazin-4(5H)thiones with a-bromoketones, bromoacetic acid, ethyl bromoacetate and bromoacetonitrile in the K2CO3—DMF system at room temperature. The composition of all synthesized compounds is in agreement with the results of elemental analysis and mass spectra. Their structure is confirmed by NMR 1H and 13C spectra. In particular, in the NMR 1H spectra of 4-arylthiopyrazolo[1,5-a]pyrazines, in addition to the characteristic signals of the pyrazole and pyrazine nuclei, signals of protons of thioaryl substituents are present in the range of 7.04 –8.05 ppm, and in NMR spectra of the 1H 4-S-methylfunctionalized derivatives of pyrazole[1,5-a]pyrazines signals of exocyclic methylene protons are present at 4.11– 5.02 ppm. Promising derivatives with antibacterial activity against the test cultures S. aureus (MIC = 7.8 g/mL), M. luteum (MIC = 3.9 g/mL), and antifungal activity against the test culture of fungus A. niger (MIC = 7.8 g/mL) were determined among 4-S-substituted pyrazole[1,5-a]pyrazines as a result of studies of the antimicrobial activity. V.I.Vernadsky Institute of General and Inorganic Chemistry 2019-02-15 Article Article Organic chemistry Органическая xимия Органічна xімія application/pdf https://ucj.org.ua/index.php/journal/article/view/22 10.33609/0041-6045.85.1.2019.58-66 Ukrainian Chemistry Journal; Vol. 85 No. 1 (2019): Ukrainian Chemistry Journal; 58-66 Украинский химический журнал; Том 85 № 1 (2019): Украинский химический журнал; 58-66 Український хімічний журнал; Том 85 № 1 (2019): Український хімічний журнал; 58-66 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/22/10
institution Ukrainian Chemistry Journal
baseUrl_str
datestamp_date 2019-04-19T09:19:07Z
collection OJS
language English
topic_facet 4-bromopyrazolo[1,5-a]pyrazines
pyrazolo[1,5-a]pyrazin-4(5H) thiones
thiophenoles
functionalized bromoalkanes
4-aryl(alkyl)thio derivatives of pyrazolo[1,5-a]pyrazines
antibacterial and antifungal activity.
format Article
author Hrynyshyn, Yevhenii
Musiichuk, Hanna
Komarovska-Porokhnyavets, Olena
Is’kiv, Oksana
Moskalenko, Nataliia
Stasevych, Maryna
Tsyzoryk, Nazar
Vovk, Mykhailo
spellingShingle Hrynyshyn, Yevhenii
Musiichuk, Hanna
Komarovska-Porokhnyavets, Olena
Is’kiv, Oksana
Moskalenko, Nataliia
Stasevych, Maryna
Tsyzoryk, Nazar
Vovk, Mykhailo
Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines
author_facet Hrynyshyn, Yevhenii
Musiichuk, Hanna
Komarovska-Porokhnyavets, Olena
Is’kiv, Oksana
Moskalenko, Nataliia
Stasevych, Maryna
Tsyzoryk, Nazar
Vovk, Mykhailo
author_sort Hrynyshyn, Yevhenii
title Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines
title_short Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines
title_full Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines
title_fullStr Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines
title_full_unstemmed Synthesis and Antimicrobial Activity of 4-Arylthio- and 4 Alkylthiofunctionalized Pyrazolo[1,5-a]pyrazines
title_sort synthesis and antimicrobial activity of 4-arylthio- and 4 alkylthiofunctionalized pyrazolo[1,5-a]pyrazines
description The reaction of pyrazolo[1,5-a]pyrazine-4(5H)ones with phosphorus tribromoxide in boiling benzene yielded 4-bromopyrazolo[1,5-a]pyrazines, and the thionation with phosphorus pentasulfide in pyridine at 90 °C led to pyrazolo[1,5-a]pyrazine-4(5H)thiones. The synthesized bromine derivatives are electrophilic, and thiones are nucleophilic substrates. Their subsequent structural modification in the first case was carried out by interaction with thiophenols, and in the second case was conducted with functional halogenoalkanes. It was shown that bromides react with substituted thiophenols in dimethylformamide in the presence of potassium carbonate at 90 °C to form 4-arylthiopyrazolo[1,5-a]pyrazines with yields of 65–83 %. 4-S-methyl-functionalized derivatives of pyrazole[1,5-a]pyrazines with yields of 60–78 % were easily obtained by the alkylation of pyrazole[1,5-a]pyrazin-4(5H)thiones with a-bromoketones, bromoacetic acid, ethyl bromoacetate and bromoacetonitrile in the K2CO3—DMF system at room temperature. The composition of all synthesized compounds is in agreement with the results of elemental analysis and mass spectra. Their structure is confirmed by NMR 1H and 13C spectra. In particular, in the NMR 1H spectra of 4-arylthiopyrazolo[1,5-a]pyrazines, in addition to the characteristic signals of the pyrazole and pyrazine nuclei, signals of protons of thioaryl substituents are present in the range of 7.04 –8.05 ppm, and in NMR spectra of the 1H 4-S-methylfunctionalized derivatives of pyrazole[1,5-a]pyrazines signals of exocyclic methylene protons are present at 4.11– 5.02 ppm. Promising derivatives with antibacterial activity against the test cultures S. aureus (MIC = 7.8 g/mL), M. luteum (MIC = 3.9 g/mL), and antifungal activity against the test culture of fungus A. niger (MIC = 7.8 g/mL) were determined among 4-S-substituted pyrazole[1,5-a]pyrazines as a result of studies of the antimicrobial activity.
publisher V.I.Vernadsky Institute of General and Inorganic Chemistry
publishDate 2019
url https://ucj.org.ua/index.php/journal/article/view/22
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