Synthesis of New Multi-Functionalised 1,1′-Carbonylbispyrazole Derivatives

Abstract

Recent research into the synthesis of bis-heterocyclic compounds, which have various practical applications, have attracted the attention of scientists. 1 Bis-pyrazole derivatives have been used as excellent inhibitors of corrosion for many metals and alloys (1, Fig. 1). [2][3][4][5] They are also used as efficient ligands in palladium-catalysed C-O and C-N cross-coupling reactions. [6][7][8][9] The bispyrazole derivatives have coordination properties to metals and are useful as catalysts, 10 for example, heteroscorpionate [RR'C(pz) 2 ] ligands derived from bis(pyrazol-1-yl)methane (2, Fig. 1). 11 The high fluorescence quantum yield of pyrazoline rings add to their wide application in selective recognition of metal ions (3, Fig. 1). 12 Bis-pyrazoles have been used in the treatment of Alzheimer's disease, brain ischaemia, heart diseases, gastrointestinal diseases, cancer, ageing and inflammation. [13][14][15][16] These compounds are also antibacterial and antifungal agents (4, Fig. 1). 17 In addition, palladium and platinum complexes of 5,5'-dimethyl-3,3'-bipyrazole and some poly substituted 1,1'-carbonylbispyrazoles have been reported as potential anti-tumour agents (5, Fig. 1). 18,19 Recently, we have investigated a new versatile route for the synthesis of 1,1'-carbonylbispyrazole derivatives 20 . In an extension of this work, we are undertaking related studies employing bispyrazole derivatives derived from pyrazole carbohydrazides. We now consider the nature of some nucleophiles and the properties of substituted methylene malonitriles which react through Michael addition-cyclisation with the subsequent construction of bis-heterocyclic compounds. Results and discussionEthyl hydrazinecarboxylate 6 reacted with substituted methylene malonitriles 7a-c in absolute ethanol to give ethyl 5-amino-4-cyano-1H-pyrazole-1-carboxylate 8a and ethyl 5-amino-4-cyano-3-methyl-1H-pyrazole-1-carboxylate 8b which have been reported previously, 20 and ethyl 5-amino-4-cyano-3-(methylthio)-1H-pyrazole-1-carboxylate 8c. They were prepared in 80-85% yield, respectively (Scheme 1). The formation of compound 8a-c was confirmed by the presence of the C=O band around 1771 cm -1 in the IR spectrum. The 1