Researcher Ateeq Rahman discusses the reduction of nitroaromatics, azides and hydrodehalogentiaon of haloaromatics using an new environmentally friendly catalyst technology
For several decades, catalysts have played an important role in the petrochemical industry and more recently they have become equally important in the fine chemical sector1. Today, heterogeneous catalysts, such as MCM-41 palladium (II) silyl amine, are quite widely used in the reduction of variety of nitro compounds2 in hydrodehalogenation reactions,3 and the reduction of azides to amines at room temperature4.
The reduction of azides to amines is an important step in organic synthesis. Removing a halogen from the molecule in organic synthesis requires an efficient catalyst that will not disturb the side chain or any important functional groups within the molecule.
The reduction of organic functional groups using metals and metal salts can be achieved in aqueous and non-aqueous solvents. In catalytic hydrogenations, metals such as palladium and raney nickel are used in the presence of hydrogen gas or a hydrogen donor. They are flammable when exposed to air and, in many cases, the use of a vacuum pump and high temperature are necessary.
Many reducing agents have been used to reduce nitro compounds with the most common being zinc, tin, or iron in the presence of an acid. Other reagents used include hydrazine, Ru3(CO)12, TiCl4-dialkyl telluride, (C2H5O)2PCl, metal hydride complexes (eg, NaBH4-NiCl4), and sulphides (eg, sodium sulphhydrate, ammonium sulphide or polysulphide).
Most chemical methods, however, lack the desired chemo selectivity over the other functional groups that are often present in the substrate - such as alkene, azide, benzyl ether, nitrile, amide, halide, and p-toluene sulphonamide.
Two classes of materials that are used extensively as heterogeneous catalysts and adsorption media are microporous (pore diameters <20Ã…) and mesoporous (20-500Ã…) inorganic solids. A major subclass of the microporous materials is that of "molecular sieves". These materials are exemplified by the large family of aluminosilicates known as zeolites in which the micropores are regular arrays of uniformly sized channels.
Considerable effort has been devoted to the frameworks with pore diameters within the mesoporous range, the largest synthesised to date being AIPO4-8, VPI-5.25, and cloverite, which have pore diameters in the range 8-13Ã….
In order to preserve the remarkable catalytic properties of the zeolites, while expanding their use to process bulkier molecules, new synthetic routes have been exploited to increase their pore diameters. Researchers have gone to significant efforts to synthesise mesoporous materials, such as silicas, or pillared clays and silicates. However, the pores in these materials are generally irregularly spaced and broadly distributed in size. Synthesis of amorphous silica-alumina with a narrow pore size distribution in the presence of tetralkylammonium cations has been reported, where the average pore diameter was related to the size of the tetra-alkylammonium cations. Although, these materials were found to be active for acid catalysed organic reactions, they were not thermally stable at high temperatures.
In 1992, researchers at Mobil Research and Development Corporation reported the synthesis of a new family of silicate/aluminate mesoporous molecular sieves (M41S) with exceptionally large and uniform pore structures. Similar to zeolite and molecular sieves synthesis, mesoporous molecular sieves are hydro-thermally synthesised by mixing organic molecules (surfactants), silica, and/or silica-alumina source to form a gel, which is then crystallised at a temperature between 70-150°C for a selected period of time. Surfactant molecules function as templates forming an ordered organic inorganic composite material.
Since the first account of the synthesis of mesoporous molecular sieves in alkaline medium appeared, a large number of publications on the synthesis of mesoporous materials, mainly MCM-41 have been reported. The synthesis of mesoporous materials has also been carried out in acidic and neutral medium.
Pinnavaia5 proposed a neutral templating synthesis mechanism based on hydrogen bonding between primary amines and neutral inorganic species. Such mesoporous molecular sieves are called hexagonal mesoporous silica (HMS).
A recently discovered family of mesoporous materials, MCM, has the potential for industrial application in fine chemical synthesis due to the fact that it is "tunable" and has a large pore size. This prompted us to design an anchored catalyst by functionalising MCM-41 with silylpropylamine and subsequent complexation with palladium.
The benefits of simple preparation, low costs, ease of handling and the efficiency of the anchored palladium complex in selective organic transformations, prompted us to explore the possibility of their use in nitro aromatics, azide and hydrodehalogenation reactions. We were able to report the successful completion of these reactions for the first time, and with excellent conversion rates.
The MCM-41 and MCM-41 Silylamine Pd (II) catalysts were prepared as reported.2-3 The Pd content of the catalyst was determined by plasma analysis (1.99%Pd). The IR spectra of the ligand and the complex showed the silylamine bands. The complex showed an additional band at 356 cm-1 indicating the presence of terminal Pd-Cl.
It is worth noting that a few important substrates have been examined for reduction of nitro compounds, such as p-nitro phenol to p-amino phenol, which is an intermediate for paracetamol synthesis, and p-nitro toluene to p-amino toluene. The bulky molecule 1-nitronaphthalene is selectively reduced to 1-amino naphthalene at room temperature. In comparison Pd/C Ru, Rh, raney nickel catalysts require high temperatures and pressures, which precludes the wide use of these reagents under such conditions.
Similar observations were made when 1-bromo naphthalene was reduced to naphthalene and 4-bromobenzaldehyde to benzaldehyde without disturbing the aldehyde group3, which remains intact. And similarly, an important molecule such as chlorobenzene is reduced to benzene which otherwise requires highly active catalysts, under high temperature and pressure.
The reduction of an azido group to an amino group has been extensively investigated because of a wide range of applications in organic synthesis, especially in nitrogen-containing heterocycles and carbohydrate chemistry. Azides are generally prepared with good stereo and enantio control and subsequent reduction permits a controlled introduction of amino function.
In our study, various azides, such as aryl, alkyl and arylsulfonyl azides, have been reduced to the corresponding amines in excellent yields at room temperature indicating a broader scope of application for our catalytic system, unlike other reagents.
A selective azide reduction was studied in the presence of other functional groups, such as carbonyl, sulphonyl, nitro and benzyl, under the same conditions. During these studies reduction of 3,4-diazido-1-pyrrolidine to the corresponding diamine was achieved without debenzylation and racemization. The catalysts can be recycled for five cycles with consistent activity, for example 3,4,5-trimethoxy phenyl azide is a model substrate.4
A major advantage of the heterogeneous catalysts systems over the homogeneous systems lies in the ease with which the catalysts can be separated after reaction. Usually, the separation of the heterogeneous catalyst from a reaction mixture is a simple matter of filtration, but the recovery of expensive homogeneous catalysts is more time-consuming and sometimes they are non-recoverable.
A simple and selective reduction of nitroaromatics, azides and hydrodehalogenation by a heterogenised homogeneous catalyst, interlamellar montmorillonite diphenylphosphine palladium (II) complex (A), was reported in good yields1.
Stringent environmental laws and cutting edge competition in the fine chemical industry has prompted demand for highly selective, eco-friendly catalytic hydrogenation of nitro aromatics and azides to amines in the presence of variety of functional groups. A catalytic method for azide reductions using inexpensive and non-polluting reagents is, therefore, highly desirable, particularly if ithe reagent can be reused.
We have demonstrated a novel inexpensive and eco-friendly method for selective nitroaromatics, azide reductions and hydrodehalogentaion by a heterogeneous MCM-41 silyl amine Pd(II) complex affording excellent yields.
The present heterogeneous catalytic system may be a potential candidate for more effiecient organic synthesis.