Взаємодією 4-бромопіразоло[1,5-a]піразинів із тіофенолами та піразоло[1,5-a]піразин-4(5Н)-тіонів із функціоналізованими бромоалканами синтезованo нові 4-арилтіо- та 4-алкілтіопіразоло[1,5-a]піразини. В ряду отриманих сполук виявленo речовини із вираженою
антибактеріальною активністю по відношенню до штамів S. aureus та M. luteum та протигрибковою дією стосовно штаму A. niger.
Взаимодействием 4-бромопиразоло[1,5-a]пиразинов с тиофенолами и пиразоло[1,5-a]пиразин-4(5Н)тионов с функционализированными бромалканами синтезированы новые 4-арилтио- и 4-алкилтиопиразоло[1,5-a]пиразины. Среди полученных соединений выявлены вещества
с выраженной антибактериальной активностью
по отношению к штаммам S. aureus и M. luteum
и противогрибковым действием относительно
штамма A. niger.
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 casewas conductedwith functional halogenoalkanes.It wasshown that bromidesreact with substituted thiophenolsin dimethylformamide in thepresence
of potassiumcarbonate at 90 °C to form 4-arylthiopyrazolo[1,5-a]pyrazines with yields of 65–83 %. 4-Smethyl-functionalized derivatives of pyrazole[1,5-
a]pyrazines with yields of 60–78 % were easily obtained by the alkylation of pyrazole[1,5-a]pyrazin4(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 spec- tra.
Their structure is confirmed by NMR 1H and
13С 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-methyl-functionalized
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.
