RICERCA ITALIANA     

Catalytic/photocatalytic oxidative activation in organic synthesis

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 catalysis and photocatalysis with oxides and oxometallates, or new hybrid organic-inorganic materials. The reactions explored include 1) the photoinduced activation of the C-H bond in alkanes and simple aliphatic derivatives, both for the selective oxidation with molecular oxygen and for alkylation reactions; 2) the mild photochemical or thermal activation at the allylic or alpha-carboxy position in aliphatic derivatives and 3) mild oxygen insertion reactions (epoxidation, Baeyer-Villiger ester synthesis and sulfoxidation). 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. Of the three collaborating units, one is mainly involved in the preparation of the new materials with (photo)catalytic activity and in developing thermal reactions, the other two in photocatalyzed oxygenation and respectively alkylation reactions, from both the preparative and mechanistic aspects. The actual significance of the methods will be pursued and assessed by using robust and reusable (photo)catalysts. <<<

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. This is a more and more difficult job with simple aliphatic derivatives that on the other hand are the cheapest and largely available feedstock. Internationally, the main approach involves the use of metal catalysts. Indeed, a large variety of transition metal complexes have been reported in recent years that operate with high selectivity and efficiency. However, these are often labile, expensive and toxic and at any rate much less used with aliphatic derivatives than with more active substrates. 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 involves 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 an 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 research projects in 2002 and 2004 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. Three research units presented the application, 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 the photoinduced activation of the C-H bond in alkanes, both for the selective oxidation with molecular oxygen and for alkylation reactions; the mild photochemical or thermal activation at the allylic or alpha-carboxy position in aliphatic derivatives for oxygenation reactions using molecular oxygen; some mild oxygen insertion reactions (epoxidation, Baeyer-Villiger ester synthesis and sulfoxidation) using molecular oxygen (in photocatalysis) or hydrogen peroxide (in thermal catalysis). 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 chemo-, regio- and stereoselectivity and higher turn over number, avoiding leaching of metal ions and inactivation. Of the three collaborating units, one is mainly involved in the preparation of the new materials with (photo)catalytic activity and in developing thermal reactions, the other two in photocatalyzed oxygenation and respectively alkylation reactions, from both the preparative and mechanistic aspects. The actual significance of the methods will be pursued and assessed by using robust and reusable (photo)catalysts.
The specific targets that the participants intend to pursue, as well as the interdisciplinary approach they mean to use, are detailed in Sec. 2.3. <<<

Timescale

24 months

National and international background

As discussed in section, the basic intuition that generated this research project is that oxidative activation may be the way for discovering novel synthetic methods that can be applied to simple aliphatic derivatives, for which mild and selective procedures are less common. Furthermore, inorganic compounds and/or supported organic compounds may be convenient activators (i.e. more robust and/or easy to manage), either in the ground or in the excited state. Thus, an interdisciplinary effort for the study of catalytic or photocatalytic process was planned. The general target of the project is developing methods that are more environment-compatible in that shorter reaction sequences, milder conditions and less aggressive or polluting reagents are used. Obviously, the present project does not cover all of possible activations of aliphatic compounds, but rather centers on some classes of reactions that are considered exemplificative. The state of the art in the specific areas chosen is illustrated below.
A major part of this research plan involves photoinduced process. Light certainly is an innocuous reagent and allows obtaining deep-seated molecular transformations under mild conditions, as it has been demonstrated in a variety of synthetic procedures [1a]. In particular, light of the near UV and visible range (i.e. sunlight) is a completely renewable source of energy; its use requires milder conditions than thermal activated reactions; it may enable to carry out chemical processes through short reaction pathways, minimizing the effects of side undesirable reactions. [1b] Two groups of photoreactions will be considered, involving respectively the activation of molecular oxygen (for oxygenations) and the activation of organic derivatives by hydrogen or electron transfer (mainly for alkylation reactions). As for the last group, the plan involves the activation of simple aliphatic derivatives, which do not absorb in the near UV. Therefore a photoactivator (P) is required that is excited by light and acts as suggested above:
P + photon à P*
P* + A-B à P(.-) + A-B(.+) or
P* + A-H à PH(.) + A(.)
The thus formed radical cation AB.+ or radical A. chemically react. If in an ensuing step of the reaction the reduced photoactivator is reduced back to the original species P (by accepting an electron or a hydrogen atom), it is not consumed and acts as a photocatalyst.
Furthermore, the specific reactions we have decided to investigate obey to the principle of ‘atom economy’. This means that, with respect to conventional syntheses, one starts from a less functionalized reagent so that some steps are skipped in the overall sequence.
As is discussed in the next section, a major topic in the proposed research plan is the formation of C-C bond by direct activation of a C-H bond. This is well known as a main problem in contemporary chemistry. Paradigmatic is the case of alkanes, where a selective method is still unavailable [2]. Methods used are based on carbocations, carbenes or, more extensively in the recent years, on organometallic derivatives and on radicals. Organometallic derivatives of alkanes are still rare [3], though a few quite interesting examples have been recently reported [4, 5], and perhaps the most promising path is that based on radicals [6]. In this field, photochemical initiation offers a potential breakthrough, in view of the mild conditions involved. Photoactivators used in the literature range from mercury vapors [7], which have obvious limitations in environmental acceptability, to organic photoactivators, which are better tuned [8], but often are consumed in the process. As for inorganic materials, from titanium dioxide to polyoxometallate salts, these are quite active and robust and can be defined photocatalysts in view of the high turn over number they reach. The last compounds have been proved to be quite active in the oxidative activation of organic molecules, including alkanes. This photocalytic activation has been long known in the literature, but has been studied mainly under the physico chemical point of view [9-11] or has been applied for the unselective degradation of organic compounds (e. g. for the elimination of organic pollutants). The synthetic application has been explored only in a limited number of cases, though attention has been called to the potential of the method and a number of satisfactory examples have been supplied [12-16]. Furthermore, these reactions are susceptible to a range of variations (e.g., inorganic templates, such as zeolites, direct the reaction path; the immobilization of photocatalysts on siliceous materials can significantly improve its activity [17, 18]). At present, the application of photocatalysis in synthesis is still limited and there is large room for improvement.
In this framework, photocatalytic oxidations using molecular oxygen have a very important role. [19] The optimisation of the photocatalytic systems in terms of efficiency and selectivity can be pursued with heterogeneous and organized systems able to control the microenvironment where the active site is placed, [20] which also favor the easier recover and recycle.
Semiconductor oxides and polyoxoanions are of particular interest, since light absorption induces the oxidation of the organic substrate and the simultaneous reduction of the oxygen molecule, [3a] finally generating highly reactive organic radicals and activates molecular oxygen with formation of intermediates such as O2-, H2O2, ROOH.
An in depth examination of literature data indicates that additional investigation is requested to optimise the photocatalytic properties of semiconductor oxides and polyoxoanions in order to achieve levels of efficiency and selectivity suitable for applied organic synthesis. Titanium dioxide is the most studied semiconductor oxide in photocatalysis, mainly because of its stability, its low cost and its capability to be employed in dispersed form. [21] Most of the work is focused on the degradation of pollutants, with some indications of the use in synthesis. [22]
Optimisation in terms of efficiency and selectivity can be pursued by: i) doping with inorganic elements of different nature in order to activate the photocatalyst in the visible region and to control the acid/base characteristics of its surface; [23] ii) creating new active sites, through derivatization on the surface [24] or the introduction of metallic nanoparticles which can be able to play a key role in the kinetics of electron transfer processes; [25] iii) controlling the competitive adsorption of intermediates formed during the photoreaction; [22b,26] iv) using solid supports and nanostructured materials in order to obtain cooperative effects among photoactive and non-photoactive sites. [27]
As for polyoxotungstates, the activity in homogeneous solution is well documented. [27] These compounds can induce electron transfer processes that lead to the reductive activation of molecular oxygen and to the formation of organic radicals. An important advantage is their ability to oxidize hydrocarbons without causing any mineralization of the substrate.
Metal oxide clusters have been anchored on the surface of micro and mesoporous silicas [28] and promising results have been obtained in the hydrocarbon oxidation by using the polyoxoanion W10O324- heterogenized. [29] Furthermore, functionalization processes involving cheap and environmentally friendly metals must be urgently tackled in catalysis. As an example, iron chloride complexes are able to catalyse the photo-oxidation of hydrocarbons. [30], e.g. of cyclohexane to cyclohexanone in aqueous emulsions of iron(III) chloride. [30a]
Another group of photoinduced reactions involves oxygenations by using molecular oxygen, in particular the photocatalyzed oxygenation of sulfides. This occurs under mild conditions, and may be the way for devising a convenient method for the (stereo)selective preparation of sulfoxides by using molecular oxygen. Electron transfer photoactivated oxidation, involving the sulfide radical cation and superoxide anion, has been shown to present a different scope with respect of the more extensively investigated singlet oxygen reaction [31], though the quantum yield is rather low at present and selectivity modest. Thus, it appears possible that the photoactivated oxidation of sulfides may be developed more extensively than presently known, in particular by using heterogeneous photocatalysis [32].
In parallel with the above photoinduced oxygenations, some thermal reactions that involve the same materials as catalysts will be examined, in order to better understand the scope and the application of the involved catalysis. In this case, the oxygen source is hydrogen peroxide. This is again represents a major goal in synthesis because of the easy availability and the environmental acceptability of this oxidant, due to the fact that the only by-product is water [33]. These systems promote a variety of oxidation reactions (the epoxidation and the ketonization of olefins, the oxidation of alcohols, the hydroxylation of aromatic compounds, the Baeyer-Villiger oxidation of ketones etc.) with exceptional activity and selectivity (including the stereoselectivity). However, while these systems may be suitable for the preparation of fine chemicals and pharmaceuticals, the obvious problem of the catalyst separation and recovery has so far hampered their use in large-scale operations. The major break-through in the use of hydrogen peroxide as oxidant in the chemical industry has been the discovery some 15 years ago of Titanium silicalite (TS-1) [34]. Further interesting results have been more recently obtained with Ti, V, Cr and Sn containing zeolites or aluminophosphates [35]. The limited number of heteroelements that can be incorporated into the structure is increased in amorphous titania-silica aerogels [36].
The site dispersion [37] is also important and can be easily controlled in crystalline mixed metal oxides, but this control is more difficult in amorphous materials produced by sol-gel technique. Moreover, the most extensively studied titania-based amorphous solids activate organic peroxides but in general fail to promote oxidation with hydrogen peroxide because of their surface hydrophilicity [38]. Finally, the surface polarity can affect not only the reaction rate and the selectivity, but also the conversion and the catalyst lifetime [39].
On the basis of these general consideration it is possible to conclude that the successful synthesis of heterogeneous catalysts for fine and pharmaceutical chemistry depends on a synergic combination between the nature of the active sites, their distribution on the surface of the support, the surface polarity and porosity.
The setting up of a large scale synthetic process depends on the evaluation and the optimisation of the above parameters. A crucial factor affecting the applicability of a given synthetic process is the great cost of the recovery and the reuse of the solvents, the reagents and the catalysts. The cost can be lowered through some strategies:
a) by heterogenizing a homogeneous catalyst
b) by using cascade or one-pot reactions
c) by using polyfunctional catalysts.
These three points find the maximum exploitation in the continuous flow synthetic processes where a further benefit is represented by the lowering of the mechanical stress of the catalyst accompanied by a growing of TON value.
One of the teams has a 10 years expertise in the preparation, characterisation and use of heterogeneous catalysts for C-C forming reactions [40] as well as in oxidation reaction including stereoselective processes [41] and two of the teams jointly obtained the photooxidation of alkanes in the presence of decatungstates [42]. Preparing tailor made heterogeneous catalysts represents a goal of numerous academic and industrial research groups and according to Corma it is today possible, through special synthetic methods or post-synthesis treatments, to prepare the solid catalyst suitable for every specific reaction [43]
The use of H2O2 as the ecocompatible and economically valuable oxidant reagent represents the common feature of the three mentioned reactions. The catalysts are available through two general synthetic routes, viz. the grafting of salts or metal complexes (Cu, Mo, V, Fe, Sn, W and Ti) on zeolitic or siliceous materials and the sol-gel technique with precursors that allows the control of the loading value. With this technique it is also possible to control the porosity and, with siliceous precursors carrying hydrocarbon chains linked through C-Si bond, to control the polarity of the catalyst surface. The physico-chemical parameters of the catalysts will also be studied such as the surface area, the acidity and acid site distribution, the surface polarity through the competitive adsorption of octane–water mixtures [38].
A great input in the catalyst performance will be achieved by in situ FT-IR studies that allow not only to recognize intermediates and chemical pathways, but also to study the interactions between reagents and reaction products with the catalyst active sites [44].
This analytical aspect assumes a great importance for optimising the synthetic process. It is indeed well known that the above mentioned advantages of the heterogeneous catalysis are frequently accompanied by a reaction rate lowering, due to a more difficult access of the active sites localized on the catalyst surface by the reagents, particularly when reactions are carried out under batch conditions. <<<