RICERCA ITALIANA     

Oxidative activation of organic molecules through new catalytic and photocatalytic processes

Università degli Studi di Pavia

Abstract

The project aims to introduce new, more environment compatible, synthetic methods for fine chemicals, based on the mild and selective activation of strong chemical bonds by photochemical reactions or catalysis and photocatalysis with oxides and oxometallates The reactions explored include 1) the activation of the C-H bond in alkanes, both for the selective oxidation with molecular oxygen and for alkylation reactions; 2) the activation of aryl C-X bonds for arylation reactions; 3) the mild oxidation at allylic or alpha-carboxy position and 4) new epoxidation and sulfoxidation methods. New materials with catalytic and/or photocatalytic activity will be prepared by heterogeneization of titanium dioxide, of other oxides and of polyoxometallates on mesoporous materials, which are characterized by greater chemoselectivity and higher turn over number, avoiding leaching of metal ions and inactivation. <<<

Principal Investigator

Angelo ALBINI Università degli Studi di PAVIA

Research Objectives

A major challenge to contemporary chemistry is developing new synthetic paths that are more environment friendly. ‘Green’ or sustainable chemistry has emerged as a discipline on its own, explicitly devoted to developing an environmental-conscious chemistry and over the past decade it has indeed demonstrated that new methodologies can be developed that protect human health and the environment. The most innovative aspect is devising new synthetic methods that start from non activated, easily available starting materials and lead through a short reactions sequence to functionalized derivatives under mild conditions, with high selectivity and minimal waste. Significant progress is being made towards this aim through the use of new catalysts. These are transition metal complexes and, while operating with high selectivity and efficiency, are often labile, expensive and toxic. The present collaborative project follows a different path, involving photoinduced reactions and some particular catalytic reactions, based on (mesoporous) oxides, which are stable materials and are active either as catalysts or as photocatalysts (or both). Light is certainly a ‘green’ reagent and there is an extensive literature on photochemistry, but the application of photochemical reactions in a ‘green chemistry’ context certainly deserves a more extended exploration. An emerging topic within photoinduced syntheses involve photocatalytic processes. In this case, a catalyst absorbs light and in the excited form activates an organic molecule, typically by transforming it into a reactive intermediate, such as a radical or a ion. These intermediates carry out the reaction of the starting material, while the catalyst comes back to the inactive state. The overall reaction requires a stoichiometric amount of photons and obviously a small amount of catalyst. Although the exploration of this method has only recently begun, there are already indication that the scope may extended and innovative. Important among such photocatalysts are some inorganic compounds such as some oxides and polyoxoanions, some of which have also a thermal catalytic activity under different conditions. A useful way for manipulating the catalytic activity of such materials, both in thermal and in photochemical process, is their incorporation in solid matrices. Thus there is an interest in an interdisciplinary work aimed to the preparation and characterization of new materials that may be used as (photo)catalysts, in parallel with the development of new (photo)catalytic processes. The realization of this fact fostered the presentation of a research project in 2002 devoted to clean synthetic methods via oxidative activation of organic substrates through novel (photo)catalytic processes, which was financed by the Italian Department of Education. The application was presented by three research units, each one with a different key interest (photochemistry, photocatalysis and heterogeneous catalysis, respectively). The same units had scientific contacts also in the green chemistry group of the Italian Interuniversity Consortium ‘Chemistry for the Environment’. The interdisciplinary collaboration in these two years plan was indeed fruitful (see the mid term report) and is now in the final phase. The encouraging results obtained and the development of the specific literature in the meantime fostered the presentation of a follow up application. As it is discussed in the detailed research plan, the main goals are as follows.
Direct activation of the C-H bond in alkanes, both for selective oxygenation reactions and for alkylation reactions, mainly via photocatalysis.
Preparation and characterization of composite heterogeneous catalysts that are effective in the epoxidation of alkenes as well as in the controlled oxidation of activated (thermally) and non activated (photochemically) sp3 carbons.
Photochemical activation of the C-halide bond in aryl halides for selective arylation reactions.
Further (photo)catalyzed mild oxidations, in particular the (entioselective) oxidation of sulfides to sulfoxides and the Baeyer-Villiger oxidation of ketones.
The specific targets that the participants intend to pursue, as well as the interdisciplinary approach they mean to use, are detailed in Sec. 2.4. <<<

First Results

It is expected that in the first phase of the project the following targets will bereached. The preparation and characterization of new photocatalysts where (doped) titanium dioxide or a polyoxotungstate are immobilized on a solid support. The development of photocatatyzed functionalization reactions of alkanes, such as controlled oxygenation and alkylation reactions. The preparation of new catalysts on mesoporous silica of on zeolites that are active in thermal allylic and benzylic oxidation reactions. The development of arylation reactions via phenyl cation photochemically generated from electron-donating substituted aryl halides.In the second phase photocatalytic methods will be extended by using the heterogeneous materials prepared in the first phase and by exploiting the chemistry of the first formed hydroperoxides as well as by exploring the oxidative bromination of alkenes and the (stereo)selective oxidation of sulfides. Methods will be developed that apply heterogeneous catalysis to the thermal alpha-hydroxylation of carboxylic acids and the epoxidation of alkenes with molecular oxygen. Photoinduced ionic arylation reaction will be developed starting from precursors different from aryl halides as well as for intramolecular applications. The results obtained will be presented in manuscripts, at least in part in collaboration between the Units, which will be submitted for publication. <<<

Timescale

24 months

National and international background

A sustainable development requires that new materials are produced that are not harmful to the environment and that are produced by methods that are environment-friendly, in that they minimize the use of available feedstock and of energy and reduce the simultaneous production of waste. Indeed the steadily growing demand for new man-made materials for new applications contrasts with the growing awareness that the limited resources available must be used in the best way and the production of waste must be minimized. A resource-saving production is thus especially important for a sustainable development (1). This is an all important challenge for contemporary chemistry. In the last decades, an extensive effort has been done by chemical companies in order to ameliorate the compatibility with the environment of the synthetic processes they are using. Clearly, much can – and must – be done by ameliorating existing technologies, but at the same time new perspectives must be opened by the exploration of new technologies. These must operate , as stated by a IUPAC Party on Synthetic Pathways and Processes in ‘Greeen’ Chemistry (2, 3), under conditions that allow to increase selectivity an minimize co-produced waste, both when actually carrying out the reaction and when separating the desired product (2, 4). On the other hand, a specific discipline, ‘green’ or sustainable chemistry has emerged and has acquired an independent status. During the past decade it has demonstrated that new methodologies can be developed that protect human health and the environment (5). Among the key issues are the use of short synthetic paths, following the principle of atom economy (6) and avoiding unnecessary protections, the use of catalysts rather than activators that are used in a stoichiometric amount, the search for mild conditions. The present project aims to contribute to the field by exploring some applications of photochemical activation and by preparing and characterizing new materials that are active both as catalysts and as photocatalysts.
As for photoactivation, it has been recently stated that ‘one of the more neglected techniques available to green chemistry is photochemistry. The use of light as an energy source, and as an agent of chemical change, can allow very mild reaction conditions, and is certainly a sustainable raw material, at least for the next few tens of millions of years’ (7). Attention to the use of photochemistry for innovative syntheses of organic molecules is demonstrated in several book and reviews (8-10), but the field certainly deserve a more extended exploration. An emerging topic within photoinduced syntheses involve photocatalytic processes (11), where a catalyst absorbs light and in the excited form activates an organic molecule, by transforming it into a reactive intermediate, such as a radical or a ion. The most used among such photocatalysts are inorganic oxides and polyoxoanions, that have also a thermal catalytic activity. An extensive research is being carried out on heterogeneous catalysts containing transition metals that are active in oxidation reaction (12). However, with these materials leaching of metallic ions to the solution or inefficiency due to the difficult access to the active sites through the micropores are a problem (13). A solution is preparing mesoporous oxides, taking care that the structure of the material does not collapse when the templating agent used to shape the channels is destroyed (14).
As for the reactions we intend to develop, an overview of the current status of the research in the field is given.
A main goal is the direct activation of the C-H bond in alkanes. As it has been recently stated, ‘a tunable, selective hydrocarbon functionalization is still out of reach and resolving mechanistic problems has proved particularly challenging’ (15). An important issue in this field is devising oxidation processes of organic substrates that use directly molecular oxygen, while achieving the required selectivity. Photocatalytic processes have an important role here, since the conditions required are much milder, and this allow to obtain a better selectivity than in thermal processes. Activation of molecular oxygen has been demonstrated and the selectivity and efficiency of photocatalysis can be increased by the use of heterogeneous of organized systems able to control the microenvironment surrounding the active sites (16,17). Semiconductors oxides, polyoxometallates and metalloporphyrins have been used as photocatalysts and are able to oxidize organic substrates while simultaneously reducing molecular oxygen to superoxide anion, hydrogen peroxide or alkylperoxides, which can take part to the oxofunctionalizaton of the organic substrate. Among these materials, titanium dioxide is a photocatalyst of great interest because of its stability, low cost and capability to be used in a dispersed form (18). These characteristics make it promising for the production of intermediates of interest in fine and industrial chemistry, e. g. of alcohols or ketones directly from alkanes and oxygen, while explorative studies are carried out for achieving the fine tuning of its activity, e. g. by doping with different metal cations (19, 20). Polyoxometallates are suitable models of semiconductor oxides and are able to participate into electron transfer processes without undergoing irreversible modifications. That these salts are able to photochemically oxidize a variety of organic compounds is well known, but up to now studies have concentrated on the physico-chemical aspects and to the detection of the first intermediates in the oxidation processes (21, 22), and only a few synthetic applications have been reported (23). In oxygenation reactions, efficiency and selectivity of these photocatalysts can be improved by using organized systems where iron porphyrin complexes act as co-catalysts (24). These materials can be immobilized on silica and indeed tetrabutylammonium decatungstate on mesoporous silica has demonstrated to be highly efficient for the selective oxidation of cyclohexane with oxygen up to 20% conversion (25). Zeolites have also been used successfully (26). An aspect that should not be undervalued is that iron porphyrin complexes can be employed to build up model systems of hemoproteins, which mimic natural enzymes such as cytochrome P-450, peroxidase, NO-synthase in the mild oxidation of hydrocarbons (27, 28).
Heterogeneous catalysts containing transition metals are active also in thermal oxidation reactions. As mentioned above, the introduction of such materials into industrial processes is limited, mainly because of the risk of leaching of metallic ions during the operation and of the difficult extension of the method to reactions involving large molecules, which do not penetrate into the pores of the catalysts, precluding activation. This has fostered the research of new macroporous materials with an exceptionally large superficial area that are better suited for the large molecules of interest as fine chemicals. As an example, zeolites containing titanium ions in their framework have been used, as it should be possible to prepare mesoporous oxides of transition metals (W, Mo, Fe, Pb, Sn and others), provided that the template used to shape the pores and channels of the materials can be removed avoiding the collapse of the structure. This has been successfully obtained for a mesoporous titanium dioxide. Application of these catalysts may be again in the oxidation of sp3 carbons, both activated (allyl or benzyl derivatives) or inactivated. Only a limited amount of work has been carried out for the first group of compounds up to now (e. g., selective oxidation of propylene (29) or of toluene (30)). More work has been devoted to the oxidation of alkanes, in view of the large availability of this low cost feedstock and the interest of the products of intermediate oxidation (alcohols, ketones, acids). Hydrogen peroxide, butylperoxide and molecular oxygen have been used as oxidants and various zeolites and silicas as catalysts. Despite some important successes (31), yields, selectivity and turn over number remain low (32). Some of these materials are used for the epoxidation of alkenes. Thus, silica supported titanium dioxide has been successfully used for the epoxidation of low-molecular weight alkenes with alkylhydroperoxides, though the reaction presently does not apply to hydrogen peroxide (33).
The oxidative activation of alkanes is not limited to oxygenation reactions. Formation of a C-C bond by direct reaction of an aliphatic C-H bond has also been explored. Photocatalysts that have been used for this aim include mercury vapors (34), which have limitations in the selectivity and in the environmental acceptability, and organic sensitizers (35), which usually require an elaborate work up. Titanium dioxide has not given satisfactory results in this field (36), but recent evidence shows that polyometallates cause efficient alkylation of electrophilic alkenes starting from alkanes (37), reaction that can be added to a few previous examples involving the addition to carbon monoxide and cyanoformates (23).
Indeed, photochemistry has the potential to activate a variety of otherwise non reactive functionalities. In parallel to the above alkylations, arylation reactions can be considered, which involve the activation of the aryl-halide bond. It is well known that these derivatives react with enolates via the SNAr path only when bearing electron-withdrawing substituents and the potentially more general SRN1 reactions often gives byproducts resulting from alternative reactions of the intermediate aryl radicals (38). Much effort has been recently given to a ‘green’ approach based on metal complexes as catalysts (38-40), but photochemistry can offer an original approach, which avoids the high price and limited stability of such catalysts. In fact, 4-chloro- ad 4-fluoroaniline undergo photochemical cleavage to give the 4-aminophenyl cation and this adds to nucleophiles such as alkenes, aromatics and heteroaromatics via a process that is the ionic analogue of the Meerwein and the Gomberg-Bachmann reactions (41, 42).
The results obtained up to now suggest that this is a viable path for a general arylation reaction.
Finally, the use of (heterogeneous) photocatalysts may open a new perspective in other reactions, e. g. in the oxidation of sulfides. With non hindered dialkyl sulfides, this can be obtained photochemically with molecular oxygen (via singlet oxygen), but carrying out the irradiation in zeolites allows to extend the reaction to diaryl sulfides (43) and likewise the use of clays (44) or of acid catalysis (45) greatly increase the scope of the reaction. The use of chiral sensitizers for the enantioselective oxidation can be envisaged. Another opportunity is the use of electron transfer photosensitizers, which have again a different scope of application (46). <<<