Novel Ring Systems: Spiro[Cycloalkane] Derivatives of Triazolo- and Tetrazolo-Pyridazines

In orderto synthesize new pyridazine derivatives anellated with different nitrogen heterocyclic moieties, spiro[cycloalkane]pyridazinones were transformed into the corresponding thioxo derivatives via a reaction with phosphorus pentasulfide. The reaction of the formed 2,3-diazaspiro[5.5] undec-3-ene-1-thiones with hydrazine provided the corresponding 1-hydrazono-2,3-diazaspiro[5.5] undec-3-ene, whose diazotization led to the desired spiro[cyclohexane-1,8′-tetrazolo[1,5-b]pyridazines. The reaction of dihydropyridazinethiones with benzhydrazide afforded the corresponding 7H-spiro[[1,2,4]triazolo[4,3-b]pyridazin-8,1′-cyclohexanes]. As a result of our work, seven new pyridazinethione intermediates were prepared, which served as starting materials for the synthesis of two kinds of new ring systems: tetrazolo-pyridazines and triazolo-pyridazines. The six new annulated derivatives were characterized by physicochemical parameters. The new N-heterocycles are valuable members of the large family of pyridazines.

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 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.

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

In this paper we report an efficient and mild procedure for the conversion of organic thiocyanates to thiols in the presence of phosphorus pentasulfide (P2S5) in refluxing toluene. The method avoids the use of expensive and hazardous transition metals and harsh reducing agents, as required by reported methods, and provides an attractive alternative to the existing methods for the conversion of organic thiocyanates to thiols.

Phosphorus Pentasulfide Mediated Conversion of Primary Carbamates into Thiols

In this paper, we report a method for the conversion of primary carbamates into thiols in the presence of phosphorus pentasulfide (P2S5) in refluxing toluene. Presently, no method exists in the literature for conversion of carbamates into thiols and, to the best of our knowledge, it is the first report for this type of conversion. This method presents an indirect route for the conversion of alcohols into thiols via their carbamate derivatives that may be useful in the total synthesis of compounds containing a thiol functionality.

3H-1,2-Benzodithiole-3-thione

The almost planar (r.m.s. deviation = 0.034 Å) title compound, C7H4S3, was synthesized by reacting 2,2-dithiodibenzoic acid with phosphorus pentasulfide in xylene solution. In the crystal, short S...S [3.3727 (14), 3.3765 (13) and 3.4284 (13) Å] contacts and aromatic π–π stacking [shortest centroid–centroid separation = 3.618 (2) Å] are observed.