*2.4.4 Reaction of Ferrocenes and Hydrazines*

Ferrocene is an organometallic compound that has excellent redox properties and may be incorporated as part of a drug's structural moiety, leading to additional therapeutic applications. Ferrocenyl compounds have shown potential as antimalarial, anticancer, cytotoxic and DNA-cleaving agents [6]. Ferrocenyl pyrazoles have also been shown to have potential therapeutic applications as well.

Recently, ferrocenyl pyrazoles **30** and **32** were prepared from ferrocenes **29** and **31**, respectively, and hydrazines in a simple two-step procedure to regioselectively give the desired 1,5-pyrazoles in good yields (**Figure 9A** and **9B**) [7].

The ferrocenyl pyrazoles **30** and **32** were then evaluated in four antimicrobial assays involving two strains each of fungi (*Aspergillus niger*, *Trichophyton rubrum*)

#### **Figure 8.**

*Synthesis of the 1,5 pyrazoles using ultrasonication and a Cu(I) catalyst [5].*

**Figure 9.** *Synthesis of ferrocenyl pyrazoles [6].*

*Synthetic Strategies and Biological Activities of 1,5-Disubstituted Pyrazoles and 2,5-Disubstituted… DOI: http://dx.doi.org/10.5772/intechopen.108923*

and bacteria (*Staphylococcus aureus*, *Klebsiella pneumoniae*). Standard antimicrobial agents fluconazole and neomycin were used in the fungal and bacterial studies, respectively. In these assays, the zone of inhibition (**Tables 1** and **2**) was measured and the corresponding minimum inhibitory concentrations (MICs) were calculated. The MIC values ranged from 85 to 95 μg/mL indicating potential as antimicrobial agents.

DNA photo-cleavage activity of the ferrocenyl pyrazoles was also evaluated using super coiled plasmid DNA by gel electrophoresis [6]. When the faster super-coiled DNA (form I) was treated with the pyrazoles, it converted to the slower-moving nicked DNA (form II), in comparison to the untreated normal DNA. These results confirmed the DNA cleavage activity of both ferrocenyl pyrazoles.

#### *2.4.5 C5-electrophilic fluorination of Pyrazoles*

The 5-fluoropyrazole core is an important structural moiety in the agrochemical and pharmaceutical industries. Synthesis of 5-fluoropyrazoles typically occurs by reaction of (i) 1,3-dicarbonyl containing CF3/CF2 (fluorinated synthon) with hydrazines followed by HF-elimination [8]; (ii) copper-catalyzed click reaction of fluorosydnones with alkynes [9]; (iii) Selectfluor and pyrazoles containing carboxylic acids followed by decarboxylation [10] and (iv) KF with pyrazoles [11, 12]. The electrophilic fluorination of pyrazoles to give 5-fluoropyrazoles was recently described using N-fluorobenzenesulfonimide (NFSI) [13]. As shown in **Figure 10** 1-substituted pyrazoles were subjected to C5-deprotonation by lithium base, which was then fluorinated using NFSI to yield 1-substituted-5-fluoropyrazoles [13].


#### **Table 1.**

*Antibacterial activities of* **30** *and* **32** *[6].*


#### **Table 2.**

*Antifungal activities of* **30** *and* **32** *[6].*

**Figure 10.** *Synthesis of 1-substituted-5-fluoropyrazoles [13].*
