The Application Of Water As A Solvent And In Conjunction With The Use Of Microwave Heating As A Tool For The Cyanation Of Aryl Halides

Aryl nitriles represent an important class of compounds since the motif is found in a range of pharmaceuticals, dyes, agrochemi-cals, and naturalproducts. They are also valuable intermediates in organic synthesis and can be easily transformed to a range of heterocycles. A number of synthetic methods for the preparation of aryl nitriles have been developed including the direct cyanation of aryl halides by copper(I)cyanide, known as Rosenmund–von Braun reaction. The classical Rosenmund–von Braun procedure can require harsh conditions, making it incompatible with sensitive substrates. While modifications to this procedure have been made palladium-, copper-, or nickel-catalyzed aryl cyanation approaches show more promise. A downside with these protocols was that toxic inorganic or organic cyanide sources such as alkali-metal cyanides trimethylsilyl cyanide or acetone cyanohydrin are often required. However, this has been overcome by the discovery that cheap, non-toxic potassium hexacyanoferrate(II), K4[Fe(CN)6] can be used as a cyanide source. Based around this discovery, a number of methodologies have been developed including some procedures using ligand-free palldium sources.If a solvent is to be used for a reaction, water is the cheapest, most abundant solvent available. It is nonflammable and nontoxic. The application of water as a solvent in organic transformations has been growing in recent years across a wide range of chemical transformations. With its special properties in terms of rate accelerations, and influence on products selectivities, or ease of product isolation, and the range of conditions such as inclusion of additives, pH range, use of biphasic systems, and high-temperature conditions that can be utilized, water will continue to play an important role as a solvent in chemical processes.Since the late 1990s the number of publications related to MAOS has increased dramatically(microwave-assisted organic synthesis). In many instances, controlled microwave heating under sealed-vessel conditions has been shown to dramatically reduce reaction times, increase product yields, and enhance product purities by reducing unwanted side reactions compared to conventional synthetic methods. The many advantages of this enabling technology have not only been exploited for organic synthesis(MAOS) and in the context of medicinal chemistry/drug discovery, but also penetrated fields such as polymer synthesis, material sciences, nanotechnology, and biochemical processes.Research in our laboratory has been focused around the application of water as a solvent for the cyanation of aryl halides, particularly in conjunction with the use of microwave heating as a tool for preparative chemistry and K₄[Fe(CN)₆] as a cyanide source:1. Cu-catalyzed cyanation of aryl halides with nontoxic K4[Fe(CN)6] was improved to be more economical and environmentally friendly by the use of water solvent and ligand-free catalyst. The reactions can be performed without any inert gas protection, which makes them more easy-handling. In addition, the suggested methodology is applicable to cyanation of a wide range of aryl iodides and activated aryl bromides, and allows the catalyst to be reused six times with a very slight change in the catalytic activity.2. A practical and environmentally benign methodology for Cu-catalyzed cyanation of aryl halides was well developed with some main innovations: the use of water as the solvent and ligand-free Cu(OAc)₂·H₂O as the catalyst under microwave heating. The suggested methodology was applicable to a wide range of substrates including aryl iodides and activated aryl bromides. In addition, the cyanated product could be quantitatively separated from the reaction mixture, and the recovered aqueous phase containing the catalyst could be reused for six times with a very slight change in the catalytic activity...