Synthesis of Azobenzenes via direct oxidation of Aryl amines using aqueous tert-Butyl HydroPeroxide

Article history: Received June 1, 2020 Received in revised form October 26, 2020 Accepted October 21, 2020 Available online October 21, 2020 A new method for the direct oxidation of aromatic amines to azobenzenes employing aqueous tertiary-butyl hydrogen peroxide and potassium tertiary butoxide as an oxidant and base, respectively is described. The desired products are obtained in good yields. The developed protocol is associated with certain advantages for example free from any metal oxidants. © 2021 Growing Science Ltd. All rights reserved.


. Results and Discussion
In order to study the suitable reaction conditions aniline was chosen as model substrate and various parameters such as oxidant, base, solvent and temperature was considered and the results are presented in Table 1. Our initial trials to convert aniline to azobenzene employing oxidants aq. 70% TBHP and 50% H2O2 were not fruitful, due to heterogeneous of starting material and reagents (Table  1, entries 1-2). Screening of other solvents such as dichloromethane, ethanol, tert-butanol, tetrahydrofuran was also not favored the oxidation reaction (entries 3-6). As shown in entry 7, a low yield of undesired side product was obtained when pyridine was used as base and solvent. Formal screening of other oxidants such as aq. 30% H2O2, O2 and NaOCl was detrimental for oxidation (entries 8-10). Then the strong base NaOH and KOH were employed in combination with acetonitrile solvent and increase of substantial amount of oxidant produced improved yield of azobenzene in 41-64%, respectively (entries 11-13). Furthermore, it was found that potassium tert-butoxide (K t OBu) was the effective base in delivering the corresponding product in 76% in acetonitrile solvent (entry 14). Having identified the optimal reaction conditions, next the scope of substrates was examined and the results are summarized in Table 2. Anilines with halide substituents, such as bromo, chloro, iodo and fluoro tolerated the oxidative conditions to afford the corresponding azobenzenes in good yields (Table 2, entries 2-5). With substrates bearing alkyl groups such as isopropyl and methyl smoothly converted to the desired products in moderate to good yield, respectively (entries 6-7). It is important to note that strong electron-withdrawing group -NO2 was highly exothermic. However, the base sensitive substituents such as -COOEt, -NHCOCH3 was not oxidized under these conditions, thus yielded the hydrolyzed product. Reaction conditions aniline (1 mmol), aq. 70% TBHP (3 mmol), K t OBu (1 mmol), acetonitrile (2 mL), 60 o C, 6 h; b Isolated yield; c The formation of products were confirmed by FTIR, 1 H-NMR and 13 C-NMR; d The formation of product was confirmed by FTIR due to reaction highly exothermic; e Corresponding hydrolysis product was observed along with starting compound.

Conclusions
In conclusion, a direct protocol for the oxidation of aniline to azobenzenes employing aq. TBHP and potassium tert-butoxide (K t OBu) as oxidant and base, respectively in acetonitrile solvent has been described. This oxidative transformation is simple and free from any transition metal catalyst. Currently, we are investigating the oxidation of more challenging substrates in our laboratory.

Acknowledgement
The author gratefully appreciates the NCHU Taiwan and the support of this work by Mekelle University, Ethiopia.

Materials and Methods
All the chemicals were purchased from Sigma Aldrich and Merck. Thin layer chromatography was also procured from Merck, which is pre-coated silica gel plates and visualized under UV light and iodine vapors. Melting points of the reported compounds were measured using DALAL instruments, India and are uncorrected. IR spectra were recorded on a Bruker Vector 22 FT-IR spectrometer operating at 400-4000 cm -1 using KBr pellets. 1 H NMR spectra were recorded at 400 MHz and 13 C NMR spectra at 100 MHz on a Bruker AVANCE FT NMR instrument using CDCl3 and DMSO-d6 as standard solvents.

General procedure for the synthesis of azobenzenes
A 50 mL round bottom flask was charged with aniline (1 mmol) followed by addition of acetonitrile 2 mL. The solution was allowed to stir at 25 o C. To this solution aq. 70% TBHP (3 mmol) was added carefully followed by addition of base K t OBu (3 mmol) and further stirred at 25 o C for 10 min. Then the whole reaction mixture was heated at 60 o C for 6 h. The oxidation process was observed by TLC. After completion of the reaction, the flask was cooled down to 25 o C followed by quenching with cold water. Then, the reaction mixture was transferred to separatory funnel and extracted with chloroform (2 × 15 mL). The combined organic layers were washed with dil. NH4Cl and water, and organic layer was dried over anhydrous Na2SO4. Obtained organic layer was evaporated under reduced pressure to give crude azobenzene. Further purification of compound was achieved by column chromatography technique EtOAc-n-hexane as eluent to yield azobenzene in 76% yield (0.140 g).