Synthesis and electrochemical properties of N-(ferrocenylmethyl)aminobenzonitrile and N-(ferrocenylmethyl)nitroaniline derivatives

Seven novel ferrocene derivatives containing (methylamino)benzonitrile and N-methylnitroaniline groups (3a-3f and 4) have been synthesized by conventional methods and characterized by FT-IR, NMR and cyclic voltammetry. The electrochemical behavior of these compounds (3a-3f) has been studied by cyclic voltammetry measurements at a platinum electrode in acetonitrile/0.1 M TBAP. The ferrocenyl group in all compounds showed similar reversible one-electron redox process, suggesting that the ferrocene moieties are equivalent and that there are no interactions among them. The formal potential, , is shifted to the more positive potential, indicating that the (methylamino)benzonitrile and N-methylnitroaniline introduced to ferrocene moiety exercise an electron-withdrawing effect.

The incorporation of (methylamino)benzonitrile and N-methylnitroaniline in a ferrocene moiety could provide new derivatives with important biological activities since several ferrocene derivatives have already been shown to be active against a number of tumors [17][18][19]. Herein we report the synthesis, characterization and electrochemical behavior of a series of N-(ferrocenylmethyl)aminobenzonitrile and N-(ferrocenylmethyl)nitroaniline derivatives which combiFne the ferrocene moiety with (methylamino)benzonitrile and N-methylnitroaniline groups.

Scheme 3. 3-(diferrocenylmethylamino)benzonitrile
The ten protons of the two unsubstituted cyclopentadienyl rings of compound 4 appear as a strong singlet at δ 4.17, whereas the protons of the methylene group appear as a singlet at δ δ4,26. The

28
ILCPA Volume 49 aromatic protons of the benzene ring are shifted downfield compared with the corresponding protons in compounds (3a-3f). 13 C NMR spectra of compound 4 show the signal of the two unsubstituted cyclopentadienyl rings at δ 69.12 and the signals of the two substituted rings between δ 68,37and 69,33.

Cyclic voltammetry study
Cyclic voltammetry measurements were performed in an electrochemical cell with a volumetric capacity of 50 mL containing a platinum working electrode of surface area 2 mm 2 , a platinum wire counter electrode of surface area 5 mm 2 , and an Hg/Hg 2 Cl 2 reference electrode (saturated with KCl). The potential was swept starting from 0 to +650 mV with a scanning rate of 100 mv.s -1 . All electrochemical experiments were carried out in acetontrile under a moisture-free nitrogen atmosphere. Tetrabutylammonium perchlorate (TBAP) was used as a supporting electrolyte.
The voltammograms of new synthesized (ferrocenylmethylamino)benzonitrile (3a-3c) and N-(ferrocenylmethyl)nitroaniline derivatives (3d-3f) in acetonitrile (10 -3 M) are shown in Fig. 1 Electrochemical studies showed shift of the ferrocene oxidation wave to more positive potentials with maximum shifts for compound 3d. All studied compounds showed one pair of redox waves corresponding to one electron transfer process. The electrochemical results of the investigated compounds were compared to that of ferrocene and summarized in Table 1.
The electrochemical parameters in Table 1 indicate that there is a significant difference between the electrochemical behaviors of compounds (3a-3f) and ferrocene. The results also indicate that the oxidation/reduction couple appears to be reversible with a separation peak of almost 71 mV (similar to that found for ferrocene under similar conditions). This value of the separation peak are, however, significantly greater than the ideal value of 60 mV for a fully reversible one-electron processes. This may be due to a combination of uncompensated solution resistance and slightly slow electron-transfer kinetics. The anodic and cathodic current intensities ratios are close to the unity which indicates the reversibility of the systems. These results also indicate a small positive shift in the formal potential values of all studied compounds. This shift can be attributed to the replacement of hydrogen atom in ferrocene by the electron withdrawing Nmethylnitroaniline groups in compounds 3a-3c and (methylamino)benzonitrile groups in compounds 3d-3f, which facilitate the redox process of compounds (3a-3f).
These results further show that the separation of the anodic and the cathodic peak potentials, ΔEp values, are almost the same for compounds (3a) and (3b), while, a small positive shift in the formal potential (33.7 mV) for compound 3a was observed compared to compound (3b). This finding confirms that the introduction of N-methylnitroaniline group in the ortho-position in compound 3a enhances the electron transfer process compared to the meta-position.  and are the oxidation and reduction wave potential; formal potential, separation peak, and are the oxidation and reduction peak currents. The potentials are listed versus SCE.
The peak current of all studied compounds (3a-3f) are markedly affected by the scan rate. The plots of versus ( = anodic peak intensity and = scan rate) for all derivatives were linear which indicates that the oxidation is Nerstian and is controlled by diffusion.

Methods
All reactions were conducted under nitrogen. Solutions were dried over anhydrous magnesium sulphate and evaporated under reduced pressure using a rotary evaporator (rotary

Physical measurements
Voltammogrames were obtained using a PGZ301 potentiostat with voltamaster 4 version 7.08 soft ware (radiometer analytical SAS). 1 H NMR spectra were recorded on BRUCKER AC 300 MHz spectrometer at 0°C, and the chemical shifts are reported in ppm relative to the central line of the triplet for CDCl 3 at 7.26 ppm. Coupling constants (J values) are reported in hertz (Hz), and spin multiplicities are indicated by the following symbols: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet). 13 C NMR and DEPT were recorded on BRUCKER AC 75 MHz spectrometer at 0°C and all are reported in ppm relative to the central line of the triplet for CDCl 3 at 77.16 ppm. The spectra reported are proton decoupled IR spectra were recorded on SHIMADZU 830-FTIR spectrometer using KBr pellets. Melting points were obtained on a Gallenkamp melting point apparatus, and are uncorrected. Column chromatography was performed using silica gel (Merck 230-400 mesh). Thin layer chromatography was performed on precoated 0.25 mm silica gel plates 60F 254 purchased from Merck.

General procedure for the synthesis of N-(ferrocenylmethyl)nitroaniline (3a-3c) and (ferrocenylmethylamino)benzonitrile derivatives (3d-3f)
The corresponding aminobenzonitrile (1.83g, 15.48 mmol) or nitroaniline (2.14g, 15.48 mmol) was added in small portions to well-stirred solution of (ferrocenylmethy)trimethylammonium iodide (6g, 15.48 mmol) in water (120 cm 3 ). The resulting mixture was then heated at 110-115°C for 6 hours. It was then allowed to cool to room temperature. The resulting precipitate was separated by filtration, washed with water to remove any trace of unchanged quaternary ammonium salt and finally recrystallized to produce the target compound.

CONCLUSION
In summary, we have successfully synthesized and characterized seven ferrocene derivatives containing N-methylnitroaniline and (methylamino)benzonitrile groups. Electrochemical studies show that the electron-withdrawing N-methylnitroaniline and (methylamino)benzonitrile groups introduced to ferrocene influence the redox potential of the iron centre. This may be due to the noninsulating effect of the methylene between the nitroaniline or aminobenzonitrile group and the cyclopentadienyl ring of the ferrocene. The electron-withdrawing character of N-methylnitroaniline decreases in the order 3a > 3c > 3b, whereas the electron-withdrawing character of (methylamino)benzonitrile decreases in the order 3d > 3f 3e.