Supramolecular interactions in biologically relevant compounds. 2-Pyrazineformamide thiosemicarbazones and some products of their cyclization

• Several heterocyclic have been prepared and characterized spectroscopically.
• Two new 1,3-thiazolidin-4-ones were obtained by microwave-assisted synthesis.
• The crystal packing of all compounds is directed by weak interactions.
• Hydrogen bonds containing the NH⋯N and NH⋯O synthons have been discussed.

Reaction of 2-cyanopyrazine with thiosemicarbazide or N-methylthiosemicarbazide afforded the (Z)-2-(amino(pyrazin-2-yl)methylene)hydrazinecarbothioamide (HPzAm4DH) and (Z)-2-(amino(pyrazin-2-yl)methylene)-N-methylhydrazine carbothioamide (HPzAm4M), respectively. (2Z,N′E)-N′-(4-Oxothiazolidin-2-ylidene)pyrazine-2-carbohydrazonamide (HPzAmot, 5) and (2Z,N′E)-N′-(3-methyl-4-oxothiazolidin-2-ylidene)pyrazine-2-carbohydrazonamide (MPzAmot, 7) have been synthesized from these thiosemicarbazones with chloroacetic or bromoacetic acids, using a conventional synthetic methodology and microwave-assisted organic reaction enhancement. The crystal structures of the thiosemicarbazones and their solvates [HPzAm4DH⋅1/2 MeOH (1), HPzAm4DH⋅H2O (2), HPzAm4M (3), HPzAm4M⋅2H2O (4)] and the 1,3-thiazolidin-4-ones (5 and 7) have been studied by X-ray diffractometry. All of the compounds were characterized by elemental analysis, mass spectrometry, FT-IR and 1H and 13C NMR spectroscopy. Several by-products have also been isolated in a crystalline form, namely 3-((Z,E)-N′-(4-oxothiazolidin-2-ylidene)carbamohydrazonium-yl)pyrazin-1-ium dibromide monohydrate, (H3PzAmot)Br2⋅H2O (6), 2-((5-(pyrazin-2-yl)-1H-1,2,4-triazol-3-yl)thio)acetic acid, (H2Pz124ttAc) (8), 2-amino-5-(pyrazin-2-yl)-1,3,4-thiadiazol-3-ium chloride monohydrate, (HPz134tda)Cl⋅H2O (9), and 2-(methylamino)-5-(pyrazin-2-yl)-1,3,4-thiadiazol-3-ium chloride N-methyl-5-(pyrazin-2-yl)-1,3,4-thiadiazol-2-amine solvate, (HMPz134tda)Cl⋅(MPz134tda) (10). The structures of these compounds were also analyzed by X-ray diffractometry. The microwave-assisted organic reaction method for synthesis is easy, convenient, and ecofriendly when compared to the traditional synthetic methods. Crystal analysis revealed that the compounds have extended 3D supramolecular networks through high levels of H-bonding and weak molecular interactions between the molecular moieties and solvent molecules. The novel synthons, which are sustained by NH⋯N and NH⋯O hydrogen bonding and other weak interactions, have been shown to assemble with 1,3-thizolidine-4-ones, 1,2,4-trizole, or 1,3,4-thiadiazole derivatives in a zigzag or herringbone architecture.

Reaction of 2-cyanopyrazine with thiosemicarbazide or with N-methylthiosemicarbazide afforded the corresponding 2-pyrazinformamide thiosemicarbazones. 1,3-Thiazolidin-4-ones derived from these thiosemicarbazones were obtained by reaction with chloroacetic acid by a conventional method and by a microwave-assisted technique. The molecular and supramolecular structures of these compounds, and the by-products obtained by the conventional method, were studied by X-ray diffractometry.Figure optionsDownload as PowerPoint slide