Amides are an important class of compounds in the chemical and pharmaceutical industry1,2. Conventionally, amides have been synthesized by the hydration of nitriles, catalyzed by strong acids3 and bases4. Many by-products such as carboxylic acids are produced due to hydrolysis of the starting nitriles and amides under these conditions. Also, several sensitive functional groups do not tolerate such harsh conditions, which results in a decrease in the selectivity of the reaction protocol. Numerous processes using homogeneous metal complexes have been reported for this hydration protocol5. However, these suffer from various drawbacks, such as difficulty in separation of product and catalyst from the reaction mixture, as well as the use of inert atmosphere for handling air-sensitive metal catalysts. Heterogeneous systems have been reported, such as alumina6, potassium fluoride-doped Al2O37 and phosphates8, silica-supported manganese oxides9, modified hydroxyapatite10, and ruthenium hydroxide coated on alumina and ferrites11. However, turnover numbers of these protocols are still small and reusability of the catalyst is intricate. A recently developed hydration protocol in pure water is good in terms of reaction conditions and product yield12, but it still needs traditional work-up using toxic organic solvents to isolate the product and uses expensive ruthenium complexes as catalysts.
Magnetic nanoparticles have emerged as a robust, high surface area heterogeneous catalyst support13. Magnetic recoverability, which eliminates the necessity of catalyst filtration after completion of the reaction, is an additional attribute of these materials. In a recent publication, we reported a simple and efficient synthesis of nano-ferrite-supported, magnetically recyclable ruthenium hydroxide [Ru(OH)x] catalyst and its application in hydration of nitriles in benign aqueous medium14.
Synthesis of ruthenium hydroxide supported on magnetic nanoparticle catalyst:
Magnetic nano-ferrite was prepared from iron sulfate and functionalization of these magnetic nanoparticles was achieved by our previously developed post-synthetic functionalization protocol, via sonication of nano-ferrites with dopamine in water for 2 h15. This step was followed by addition of ruthenium (Ru) chloride at a basic pH; Ru(OH)x catalyst on the amine-functionalized nano-ferrites was obtained in good yield (Figure 1).
The catalyst was characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM), which confirmed the formation of single-phase Fe3O4 nanoparticles with spherical morphology and a size range of 11-16 nm, which is comparable with the crystallite size calculated from X-ray spectrum using Scherer formula (11.52 nm). FT-IR confirmed the anchoring of dopamine on ferrite surfaces. The signals of Ru and Ru(OH)x were not detected in XRD due to the highly dispersed low percentage of Ru in the sample. The weight percentage of Ru was found to be 3.22% by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis.
Hydration of nitriles in aqueous medium using microwave irradiation:
Ruthenium hydroxide supported on magnetic nanoparticle catalyst was then tested as a catalyst for hydration of nitriles in aqueous medium as a benign solvent, under microwave (MW) irradiation conditions (Figure 2). MW-assisted chemistry was used due to the efficiency of the interaction of the polar nano-catalyst and water molecules with microwaves. The reaction mixture was rapidly heated to requisite temperatures under MW irradiation with precise control of the reaction temperature16.
This catalyst showed high activity for hydration of benzonitriles. The entire protocol was carried out in pure water without using any organic solvent even in the product work-up step. The use of MW-irradiation expedited the reaction and excellent yield of benzamide was obtained within 30 minutes.