CHAPTER 1: Homogeneous, Heterogeneous and Nanocatalysis

For the conversion of raw materials into fine chemicals and high-value building blocks, reliable oxidation methods have been found to be indispensable tools in modern organic synthesis.^1–6  Various methods with remarkable efficiencies have been developed for a wide array of oxidative transformations which are now well established. However, since most of these standard protocols rely on the use of hazardous terminal oxidants or cause the generation of significant amounts of waste products, there is still an evident need for methodological improvements with respect to environmental and economic issues. Especially in terms of waste product minimization and the use of renewable materials, catalytic aerobic transformations offer some ideal features of a ‘green’ process⁷  towards sustainability. In particular, the oxidation of alcohols is one of the most important synthetic operations in both the organic chemistry laboratory and the chemical industry. Although classic oxidation reactions can be very efficient and selective, they often involve the use of stoichiometric reagents and halogenated solvents, resulting in the generation of large quantities of wastes.⁸  The urgent need for more sustainable chemical processes has prompted the development of mild and selective oxidation methods based on the use of green reagents and solvents. In this context, the direct use of oxygen as an oxidizing reagent is a very desirable feature for modern synthetic methods. Hence new catalysts for the aerobic oxidation of alcohols have attracted much attention in recent years. Transition metal-based systems have been successfully used for the aerobic oxidation of alcohols to the corresponding carbonyl compounds with excellent performances of several transition metal catalysts.^5,9 

Homogeneous, heterogeneous and nanocatalysis are the subject of intense research in this field and, rather than aspiring to be exhaustive, this chapter deals with the comparison of those macro-areas within the context of efficiency in reaction design, by following the principles of green and sustainable chemistry for oxidation processes.

The latest advances in homogeneously catalyzed aerobic oxidation have recently been reviewed for oxovanadium,¹⁰  palladium,¹¹  copper complexes¹²  and bifunctional molecular catalysts.¹³  Moreover, cooperative catalysis, combining transition metals with either 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or other nitroxyl radicals has been gaining in importance.^5,14  At the same time, as a result of their redox–amphoteric properties, significant progress has been made in the development of metal-free aerobic oxidation processes based on TEMPO and related nitroxides as transition metal surrogates.¹⁵  The wealth of papers (more than 140 within the past 3 years) on tailored homogeneous catalysts for the aerobic oxidation of alcohols demonstrates the great efforts being undertaken in this field. The complete history of the selection of metals such as copper, ruthenium, palladium, gold and vanadium is exhaustively explored in later chapters; here, however, we summarize the recent advances in this field by describing some representative examples that follow the principles of rational design of homogeneous catalysts along with the fundamentals of the green and sustainable chemistry already mentioned in the introductory section: (i) oxidizing in good yield with broad functional group compatibility; (ii) achieving high selectivity, if possible without the use of protecting groups; (iii) using non-halogenated solvents, with water being best; (iv) considering safety and using air instead of pure oxygen as the oxidant; and (v) taking into account the ecotoxicity and atom economy of the process.

Copper¹⁶  and, more recently, iron salts¹⁷  in combination with particularly persistent nitroxide as the active oxidation catalyst proved to be superior systems for homogeneous catalyzed alcohol oxidation under an O₂ atmosphere.⁵  Extensive descriptions of the history and development of this subject can be found in Chapters 2 and 6. In any case, copper/TEMPO and related systems deserve a brief introduction in order to understand their important role in sustainable developments in homogeneous catalysis. Recent advances reported by Stahl and co-workers¹⁶  demonstrated that the (bpy)Cu(i)/TEMPO catalyst system with NMI (bpy=2,2′-bipyridine, NMI=N-methylimidazole) overcomes nearly all of the limitations associated with Pd(ii) catalysts. This catalyst system permits the chemoselective oxidation of benzylic, allylic and aliphatic primary alcohols to the corresponding aldehydes, with rates at least one order of magnitude higher than those observed with Pd(ii) catalysts. Moreover, this method is compatible with substrates bearing diverse functional groups and uses ambient air as the source of the O₂ oxidant. A significant rate enhancement has been found with the replacement of Cu(ii) with a Cu(i) source and the catalyst system in Scheme 1.1 is notable for its efficiency in the oxidation of aliphatic alcohols.

Mechanistic investigations^16f support a two-stage catalytic mechanism consisting of (1) ‘catalyst oxidation’ in which Cu(i) and TEMPO–H are oxidized by O₂ via a binuclear Cu₂O₂ intermediate and (2) ‘substrate oxidation’ mediated by Cu(ii) and the nitroxyl radical of TEMPO via a Cu(ii)–alkoxide intermediate (Scheme 1.2). Catalytic rate laws, kinetic isotope effects and spectroscopic data show that reactions of benzylic and aliphatic alcohols have different turnover-limiting steps. Catalyst oxidation by O₂ is turnover limiting with benzylic alcohols, whereas numerous steps contribute to the turnover rate in the oxidation of aliphatic alcohols.

Another excellent study by Stahl et al. explored in depth the substrate scope and the applicability of different nitroxyl co-catalysts, particularly evidencing the complementary role of TEMPO versus ABNO (9-azabicyclo[3.3.1]nonane N-oxyl).¹⁸  A catalyst system consisting of (MeObpy)Cu^I(OTf) and ABNO (MeObpy=4,4′-dimethoxy-2,2′-bipyridine) mediates the aerobic oxidation of all classes of alcohols, including primary and secondary allylic, benzylic and aliphatic alcohols, with nearly equal efficiency. The catalyst exhibits broad functional group compatibility and most reactions are complete within 1 h at room temperature, using ambient air as the source of oxidants. Whereas Cu(i)/TEMPO shows high chemoselectivity for primary alcohols, allowing excellent steric discrimination between unprotected primary and secondary alcohols and also primary alcohols in different steric environments, Cu(i)/ABNO is equally effective with all classes of alcohol substrates. Together, these catalytic systems provide compelling aerobic alternatives to traditional alcohol oxidation methods. This Cu(i)/ABNO protocol is also suitable for larger-scale applications; 10–50 mmol (1–9 g) of selected alcohols produced the desired products in ≥90% yield in an open-reaction flask at room temperature within 1–3 h. On the other hand, several drawbacks due to catalyst deactivation require further attention (reactions with a 1 mol% MeObpy/Cu loading suggest that the catalyst deactivates before reaching full conversion of the substrate).

Following the route indicated by the rational design well defined in the work of Stahl and co-workers,¹⁶  in this first section devoted to homogeneous catalysis, the most recent examples of aerobic oxidation are described in two subsections. The first concerns the ligand design and the second focuses on the use of fine-tuned homogeneous catalytic systems for the one-pot synthesis of high-value products such as heterocyclics or nitrogen-containing compounds which are suitable either as building blocks or for fine-chemical synthesis.

Many different ligands – such as pyridine, N-heterocyclic carbene chelated N-O-, N-N-, tridentate, pincer and tetradentate ligands – are used for the preparation of copper, palladium and iron complexes which are active in the aerobic oxidation of alcohols.

N-O-dentate ligands for copper-catalyzed alcohol oxidation under air or oxygen conditions were first investigated by Punniyamurthy and co-workers, who used a salen analog N-O-ligand to achieve the efficient oxidation of primary alcohols to the corresponding aldehydes under oxygen conditions.¹⁹  In this field, Ding and co-workers recently reported highly efficient performances – in particular for secondary alcohols – of the commercially available and inexpensive N-O-bidentate ligand l-proline under mild conditions (Scheme 1.3).²⁰  When using 5 mol% of Cu(i) as the metal precursor, in the presence of 5 mol% of TEMPO as the co-catalyst and air as the oxidant, a wide range of primary and secondary benzylic alcohols are transformed smoothly into corresponding aldehydes and ketones with high yields and selectivities in DMF at room temperature.

Well-defined palladium complexes of the type [Pd(N–O)(X)(L)], in which N–O is an anionic chelate, L is a monodentate base and X is a generic anionic ligand, are attractive catalysts for aerobic alcohol oxidation because they contain within themselves the essential elements to generate catalytic activity. Cámpora and co-workers²¹  developed a versatile synthesis that provides access to a wide variety of neophylpalladium complexes of the type [Pd(CH₂CMe₂Ph)(N–O)(L)], where N–O is picolinate or a related N-O-bidentate, monoanionic ligand (6-methylpyridine-2-carboxylate, quinoline-2-carboxylate, 2-pyridylacetate or pyridine-2-sulfonate) and L is pyridine or a pyridine derivative. These complexes promote the aerobic oxidation of benzylic, allylic and aliphatic alcohols by oxygen. The chelating N-O-ligand is the key element in ensuring the stability of the catalyst and controls the stereoelectronic properties of the active center. Furthermore, the carboxylate group imparts bifunctional character to this ligand, facilitating proton transfer from the substrate (alcohol) to the final electron acceptor (oxygen). The co-ligand L also plays an important role. It must be labile enough to generate the coordinative unsaturation required to allow catalytic activity, but at the same time it contributes to the stability of the system, preventing excessively rapid catalyst decay. Among the different co-ligands tested, pyridine itself showed the best balance of these two properties. Whereas the oxidation of benzyl and secondary aliphatic alcohols with pyridine–carboxylate catalysts is highly selective, carboxylic acids are produced in the case of the primary aliphatic and allyl alcohols. Since the activity and selectivity of these catalysts are ligand controlled, it is expected that the catalyst design may be tuned to improve activity, selectivity and resistance to aggressive oxidation conditions or to generate desirable properties such as compatibility with water or other environmentally friendly solvents. Another useful property of this system is that catalysts perform without additives, facilitating product separation and purification.

With regard to N-O-vanadium(v) complexes, 8-hydroxyquinolinates have recently been extensively investigated by Hanson and co-workers for the vanadium-catalyzed aerobic oxidation of lignin model compounds, including benzylic, allylic and propargylic alcohols (Scheme 1.4).²²  The vanadium complex (HQ)₂V(O)(OiPr) (2 mol%, HQ=8-quinolinate) and NEt₃ (10 mol%) catalyze the oxidation of benzylic, allylic and propargylic alcohols with air. The catalyst can be easily prepared under air using commercially available reagents and is effective for a wide range of primary and secondary alcohols. Reactions proceed under mild conditions (air, 40–80 °C) and in a variety of solvents.

Neutral and cationic pyridine-based palladium compounds have been developed by Oberhauser and co-workers as efficient catalysts for the atom-economic aerobic oxidation of unprotected diols to yield chemoselectively the corresponding hydroxy ketone.²³  A comparative catalytic study showed that the bis-cationic precursor (Figure 1.1), in combination with an external base (i.e., K₂CO₃) in a 19:1 v/v toluene–DMSO solvent mixture, outperforms neutral complexes. The efficiency of bis-cationic catalyst precursors has been found to depend on (i) the coordination properties of the diol employed with respect to Pd(ii) (e.g., 1,2-diols show higher conversion than 1,3-diols) and (ii) the bulkiness and coordination properties of the counterion (e.g., the OTs precursor showed the highest catalytic activity and the BAr₄ counterpart the lowest).

The use of palladium NCN and CNC pincer complexes have been found to be effective in the aerobic oxidation of secondary benzyl alcohols at atmospheric pressure in PEG-400, a sustainable reaction medium with excellent yields and functional group tolerability²⁴  (Scheme 1.5). The recycling of active catalytic species is performed up to the fifth run, while catalyst loadings decreased to 10⁻⁸ mol%, thus achieving significant turnover number (TON) and turnover frequency (TOF) values. The same conditions proved to be effective for the aerobic oxidation of benzyl methylene compounds, a little-explored process, by palladium catalysts.

Following the pioneering work of the groups of Sheldon,²⁵  Reedijk²⁶  and Repo²⁷  on the use of Cu-based, water-tolerant oxidation catalysts, Pombeiro and co-workers recently developed several copper complexes for the TEMPO-mediated aerobic oxidation of alcohols in water.²⁸  Catalytic processes in aqueous media may require constrained active particles in the aqueous phase and the design of homogeneous water-soluble catalysts usually involves the use of a suitable ligand with a hydrophilic function.²⁹  In most cases, such a ligand can be obtained by attaching a water-solubilizing group, e.g. a sulfonate or carboxylate group. Another major challenge is the reversible tuning of the acid–base properties of the catalyst, which can enhance the activity/selectivity towards a certain product and/or reversibly change the hydrophilicity. In addition, many processes require a certain pH interval. Therefore, a complex is needed that, in addition to its main catalytic function, can maintain the pH within a certain range (i.e. have buffer properties). Hence the synthesis of water-soluble complexes with several pH-tunable sites for protonation–deprotonation is of interest for new green catalytic processes. In this field, the coordination chemistry of copper has been explored with N-ethyldiethanolamines for the formation of dicopper(ii) alkoxo-bridged complexes using a self-assembly method.²⁸  Azo derivatives of β-diketones (ADBs) – in particular o-hydroxy-substituted ADBs³⁰  and their congeners – contain sites for possible pH regulation properties, especially sulfo and amino groups such as 3-(5-chloro-2-hydroxy-3-sulfophenylhydrazo)pentane-2,4-dione.³¹  All of the above-mentioned systems have shown to be significantly active in the aerobic TEMPO-mediated oxidation of benzyl alcohols to aldehydes. A more recent study investigated the template formation of alkoxy-1,3,5-triazapentadien(e/ato)copper(ii) complexes:³²  the latter are active in the oxidative conversion of primary and secondary alcohols to the corresponding carbonyl, making possible molar yields of aldehydes of up to 100% with >99% selectivity. Reactions were carried out in a basic (K₂CO₃) aqueous medium, without any organic solvent and under atmospheric pressure of air (or O₂), with high yields and selectivities. Those mild conditions are of industrial significance.

Safari and co-workers introduced a new selective, economical and efficient aerobic pathway for the selective photo-oxidation of a variety of aromatic and aliphatic alcohols to the corresponding aldehyde and ketone derivatives.³³  Their method uses molecular oxygen (1 atm pressure of air) in the presence of free base porphyrins and metalloporphyrins as sensitizers (Sens*) and white light or sunlight in CH₃CN at room temperature. Scheme 1.6 shows the structures of the sensitizers used and the reaction conditions. This method is broad in scope, exhibits chemoselectivity and proceeds under mild reaction conditions. The resulting products are obtained in good conversions within a reasonable time. The best results with both primary and secondary alcohols were obtained with metallated H₂TMP and iron–porphyrins ClFeTMF.

Transition metal species (ML_x, M=Co, Fe, Cu, Mn, Ni), which are usually used in the form of metalloenzymes, synthetic porphyrins and Schiff base complexes, may activate dioxygen for aerobic oxidations.³⁴  The structure of the majority of these complexes includes cyclic N₄ or open-chain N₂O₂ donor equatorial ligands. Within this field, the simple and inexpensive ligand dimethylglyoxime (DH₂), in combination with cobalt nitrate and TEMPO, efficiently accomplished the aerobic oxidation of various alcohols (including primary and secondary benzylic, allylic and aliphatic alcohols), which were quantitatively converted to the corresponding aldehydes or ketones at 70 °C under 0.4 MPa dioxygen pressure.³⁵  Several other metal salts (based on Co, Cu, Fe, Mn and Ni) and reaction conditions were screened, but led to poorer results. Mechanistic investigations shed light on the role of the three-component Co(NO₃)₂/DH₂/TEMPO catalyst. During oxidation, the in situ-generated cobaloxime and NO_x played crucial roles in the activation of dioxygen, thus resulting in two concerted catalytic pathways: cobaloxime-activating-dioxygen TEMPO-catalyzed and NO-activating-dioxygen TEMPO-catalyzed aerobic oxidation of alcohols. Therefore, the present system could efficiently catalyze the aerobic oxidation of aliphatic and secondary alcohols without the need for an additional base.

Within the scope of the oxidative kinetic resolution of secondary alcohols (OKR),³⁶  a naphthoxide-bound iron(salan) complex has been recently reported as a good example of an efficient iron-catalyzed aerobic oxidative kinetic resolution of secondary alcohols.³⁷  The substrate scope was studied with secondary alcohols in the presence of several phenol derivatives, which are reluctant to undergo oxidative coupling, with good to high enantiomeric differentiation using molecular oxygen. The ligand plays the main role [the iron(salan) complex itself is inactive] and the modified complex represents a step forward in the iron-catalyzed aerobic kinetic resolution of secondary alcohols (Sekar and co-workers reported iron-catalyzed OKR using O₂ as the terminal oxygen, but the substrate was limited to benzoins and a catalytic amount of TEMPO was necessary³⁸ ).

Various N-N-ligands such as phenanthroline-based ligands have been investigated. For copper catalysts, the electronic properties of the supporting ligand have been shown to affect the catalytic efficiency, identifying electron-rich 1,10-phenanthroline derivatives as better catalysts for the aerobic oxidation of alcohols.³⁹  On the other hand, for palladium catalysts, the oxidative degradation of the ligand has been confirmed as an ‘Achilles heel’ due to the rapid deactivation of the catalysts.⁴⁰  The longer catalyst lifetimes of Pd complexes bearing the 2-CF₃-substituted ligand 4-methyl-2-(trifluoromethyl)-1,10-phenanthroline (tfmm-phen) reveal that the inhibition of ligand oxidation can lead to stronger catalysts for aerobic alcohol oxidation. Nevertheless, the modest TON observed (22 mol ketone per mol of Pd) suggests that other decomposition pathways may limit the lifetime of catalysts derived from tfmm-phen.

As potential alternatives to traditional nitrogen and phosphine ligands, N-heterocyclic carbenes (NHCs) have attracted great interest owing to their unique properties.⁴¹  The performance of NHCs is easily tuned through the introduction of various functional groups at the N-positions.⁴²  Chen and co-workers reported TEMPO-functionalized imidazolium salts which react with commercially available copper powder to produce Cu–NHC complexes.⁴³  The in situ-generated Cu/NHC/TEMPO complexes are fairly efficient catalysts for the aerobic oxidation of primary alcohols to aldehydes (Scheme 1.7). The catalyst is easily available and various primary alcohols were selectively converted to aldehydes in excellent yields. Structural changes to the catalyst in the catalytic cycle are unclear. It was difficult to isolate the catalyst after oxidation was complete because of the low catalyst loading and good solubility. To understand fully the catalytic performance, further work is needed.

Cazin and co-workers⁴⁴  reported on a series of Pd(0) complexes bearing mixed ligand systems, NHC/PR₃, which react cleanly with O₂, forming peroxo complexes [Pd(η²-O₂)(NHC)(PR₃)]. [Pd(NHC)(PR₃)] complexes are used as pre-catalysts in the oxidation of alcohols at a low catalyst loading (0.25 mol%) under mild conditions (60 °C and 1 atm of O₂). Additives such as acetic acid and molecular sieves have a major effect on the reaction outcome. In the case of the most reactive substrates, oxygen can be replaced by air.

The one-pot synthesis of valuable chemicals such as heterocyclics, imines and nitriles from alcohols and a nitrogen source is another challenging perspective of green homogeneous catalysis. Various single-step or tandem reactions with mono- or multicomponent catalysts which exploit the aerobic oxidation of alcohols are steps forward in the concept of ‘greener’ homogeneous processes.

By exploiting the biomimetic approach developed by Bäckwall and co-workers – which combines a ruthenium catalyst (Shvo complex), a cobalt–salen complex and a benzoquinone – the ruthenium catalyst can efficiently catalyze the aerobic oxidation reactions of alcohols⁴⁵  and amines⁴⁶  to give the corresponding ketones and imines, respectively. Recently, the scope of this biomimetic catalytic system has been expanded, demonstrating that diols and amino alcohols can be oxidized to lactones⁴⁷  and lactams,⁴⁸  and that the oxidative coupling of benzylamines and 2-aminophenols makes possible the synthesis of benzoxazole structural elements into natural products and building blocks for pharmaceuticals and organic materials (Scheme 1.8).⁴⁹ 

The proposed mechanism is reported in Scheme 1.9.

This biomimetic system can be applied to the synthesis of benzimidazoles and benzothiazoles and was applied to the synthesis of benzoxazoles in the same way. This biomimetic approach should be a useful method for the synthesis of pharmaceutically important heterocyclics under environmentally benign reaction conditions.

Another recent report on the preparation of benzimidazoles, benzoxazoles and benzothiazoles directly from aromatic alcohols and o-phenylenediamine, o-aminophenol and o-aminothiophenol exploits a simple but efficient Cu(I)/TEMPO/Bpy catalytic system under ambient conditions (Scheme 1.10).⁵⁰ 

N-Heterocycles can also be prepared using alcohol oxidation as a key synthesis step. The potential of the Cu/TEMPO/O₂ catalytic system as an aerobic oxidation catalyst was explored by Cook and co-workers for the synthesis of substituted indoles and quinolones.⁵¹  Different Cu(i) and Cu(ii) salts, N-N-ligands (such as 2,2′-bipyridine and 1,10-phenanthroline), bases and TEMPO combinations were screened. The study indicated that the Cu/TEMPO oxidation catalyst has the potential for the synthesis of N-heterocyclics. In the case of indole synthesis, the issue of product inhibition needs to be resolved. The kinetics suggest that the formation of the product is faster than the inhibition reaction that leads to the catalyst deactivation. There is room for expansion of the substrate scope, especially for those containing both primary and secondary alcohols.

Ma et al. developed a general and practical iron nitrate/TEMPO-catalyzed aerobic oxidation of the alcohols most commonly used in academic and industrial laboratories, such as primary and secondary alkanols, benzylic, allylic and propargylic alcohols and allenols, efficiently expedited by a catalytic amount of sodium chloride.⁵²  Subsequently, the same Fe(NO₃)₃/TEMPO/NaCl system was efficiently used in the aerobic oxidation of (i) propargylic alcohol to α,β-unsaturated alkynals and alkynones,⁵³  (ii) allylic alcohols with retention of the CC double-bond configuration⁵⁴  and (iii) indole carbinols (an important unit in organic synthesis, since a large number of indole carbonyls with bioactivity can be found in natural products) (Scheme 1.11).⁵⁵  The practical use of these preparations was also verified on a large scale (0.1 mol or 1 mol of selected substrates) by using toluene as solvent and purifying the products by distillation or recrystallization, with 90% isolated yield.

Imines are useful compounds for organic synthesis of pharmaceuticals and agricultural chemicals. Traditionally, imines are synthesized by the condensation of aldehydes (or ketones) with primary amines. The required carbonyl compound is generally prepared by the oxidation of the corresponding alcohol. With a view to creating environmentally benign processes, the development of catalytic systems for tandem reactions has attracted considerable attention. From this standpoint, oxidative coupling of alcohols and amines should be the most direct way to produce imines. The dicopper complex [Cu₂(bpnp)(μ-OH)(HCOO)₃] (Scheme 1.12), stabilized by the bpnp ligand, is an example of an efficient catalyst for the oxidative coupling of alcohols with amines to yield the corresponding imines in the presence of oxygen under solvent-free conditions.⁵⁶  Even though more detailed studies are needed to study the effect of the metal centers, this method holds the promise of general applicability, producing good yields of products with various benzyl alcohols and amines, low catalyst loading and solvent-free reaction conditions.

Yu and co-workers reported on the palladium-catalyzed aerobic oxidative synthesis of imines from alcohols and amines under ambient conditions (Scheme 1.13).⁵⁷  Ligand, TEMPO and base proved to be key factors for the reaction and, from a detailed screening, the best results were obtained with Pd(OAc)₂, TEMPO and Et₃N as the base. The imine synthesis occurs in one pot from alcohols and amines via a low-loading palladium-catalyzed tandem aerobic alcohol oxidation–dehydrative condensation reaction that can be readily carried out in open air at room temperature. The same group also reported findings in the area of air-promoted metal-catalyzed aerobic N-alkylation.⁵⁸  Their method is rather general in catalyst and substrate scope and uses many simpler, cheaper, readily available ligand-free metal catalysts and a wide range of amines, amides and alcohols which behave with respect to activities more effectively than those under conventional anaerobic conditions. Although a few N-alkylation reactions have been carried out under aerobic conditions and found to be more efficient than the anaerobic reactions, the role played by air in such reactions remains to be fully elucidated.

Nitriles are widely used in both chemical and biological applications as they can be important building blocks in the pharmaceutical, fine chemical, dye and agrochemical industries. However, despite the potential usefulness of their available synthetic protocols,⁵⁹  the use of toxic solvents and expensive reagents along with the production of large amounts of inorganic waste and tedious work-up procedures limit their application from a green chemistry perspective. The oxidative conversion of alcohols to nitriles is an attractive alternative and the development of a highly efficient and environmentally benign solvent-free protocol is still a challenging task. As an example, Bhanage and co-workers exploited a copper catalyst for the aerobic oxidative reaction of benzylic and allylic alcohols, using ammonium formate as the nitrogen source, for the synthesis of nitrile compounds under an air atmosphere and solvent-free conditions (Scheme 1.14). A wide range of substrates were well tolerated in the reaction, which produced water as a by-product.⁶⁰  From a green perspective, the developed protocol uses an inexpensive and readily available CuCl₂·6H₂O catalyst; the system circumvents the use of oxidants such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), I₂, H₅IO₆ and 1,3-diiodo-5,5-dimethylhydantoin (DIH) and the use of a handy and inexpensive nitrogen source such as ammonium formate.

Transition metal catalysis, organocatalysis and biocatalysis have attracted much attention in the field of organic synthesis because they can provide highly complex molecules in addition to good chemo-, regio- and stereoselectivity. In recent years, dual catalytic systems, which combine different catalytic species among transition metal complexes, organic catalysts and biocatalysts, have been reported for multifunctionalization and multistep, one-pot reactions.⁶¹  Although a number of multicatalytic reactions using both organocatalysts and transition metal catalysts have been implemented and their powerful advantages described, one of the limitations of dual metal–organocatalytic reactions is that the rigorous reaction conditions require an inert atmosphere and purified solvents to maintain the reactivity of the transition metal catalyst. Jang and co-workers⁶²  combined an aerobic copper-catalyzed oxidation with an organo-catalyzed Michael addition reaction (iminium catalysis). By controlling the amount of TEMPO, allylic alcohols were converted into β-substituted aldehydes and α,β-substituted aldehydes in good yields and with excellent levels of stereoselectivity, extending the substrate scope of α,β-unsaturated aldehydes to low molecular weight aliphatic alcohols in addition to aromatic alcohols (Scheme 1.15). Furthermore, merging iminium and enamine catalysis provides a highly stereoselective protocol for the formation of α,β-substituted aldehydes as a single diastereomer with remarkably high enantioselectivity. Large amounts of solvents and silica gel to purify the resulting aldehydes are not required.

Traditionally, alcohols could be converted into esters by multiple steps. However, the direct conversion of alcohols to esters in the presence of catalysts may represent a step forward towards green, economic and sustainable processes. Despite the fact that great attention has been paid to the palladium-catalyzed selective oxidation of alcohols to aldehydes in recent decades, reports on the oxidative esterification of alcohols are scanty. The first palladium-catalyzed direct aerobic oxidative esterification of benzylic alcohols with methanol and various long-chain aliphatic alcohols was reported by Lei et al.⁶³  Benzylic alcohol and methanol were used in the model reaction and molecular oxygen was used as oxidant. The applicability of this method, where [PdCl₂(CH₃CN)₂] with NaOtBu gave the best results in MeOH as solvent, was shown for a range of different substrates to give their corresponding esters in moderate to high yields. The challenging esterification reactions of long-chain aliphatic alcohols were accomplished by using a P-olefin ligand to control the selectivity. The direct nature of this route and the use of O₂ as oxidant represent a step towards an environmentally benign and sustainable process.

Even through heterogeneous catalysts are preferable to homogeneous ones owing to their easier recovery and reuse, there are still some concerns and practical problems in the use of heterogeneous catalysts in the aerobic oxidation of alcohols owing to lower catalytic activity and deactivation.^64,65  Nevertheless, the heterogeneous approach is highly desirable for commercial applications and recent reviews have dealt with the subject of liquid-phase oxidation of alcohols over supported transition metals.^65,66  This section summarizes the latest research regarding heterogeneously catalyzed processes for alcohol oxidation in the liquid phase; however, the reader interested in this wide field is referred to the authoritative papers cited above for further details.

Heterogeneous, late transition metal catalysts – notably ruthenium, gold, platinum and palladium supported catalysts – are particularly active for the liquid-phase aerobic oxidation of alcohols, but other metals and metal compounds have also been studied recently, including Ag⁶⁷  and Co₃O₄.⁶⁸ 

Cinnamyl alcohol (CA) and benzyl alcohol (BA) oxidation are often used as model reactions. As with other alcoholic substrates, CA and BA oxidations generally proceed through an aldehyde intermediate to the final acid products. These two molecules are both highly reactive and the CC bond present in the CA molecule may undergo side reactions, forming 3-phenylpropan-1-ol, 3-phenylpropionaldehyde and 3-phenylpropanoic acid (Scheme 1.16). In fact, apart from the oxidation pathway, side reactions due to hydrogen transfer and hydrogenolysis, depending on the reaction conditions and the catalyst used, can be observed. As an example, the side reaction forming 3-phenyl-1-propanol is typical for allylic alcohols and may be considered a transfer dehydrogenation reaction in which the reactant plays the role of hydrogen acceptor.⁶⁹ 

Benzyl alcohol was also reported to be subjected to different reactions depending on the catalyst used and the reaction conditions (Scheme 1.17). Indeed, in addition to the oxidation of BA to form benzaldehyde and benzoic acid and benzoate, reactions such as (i) disproportionation to form toluene, benzaldehyde and H₂O and (ii) dehydration to form dibenzyl ether have been reported.⁷⁰ 

Particle size-dependent catalytic activity has been reported for BA and CA oxidation over metals such as Pd, Pt and Au. The optimum particle size was identified as around 3–5 nm, indicating that the reaction is structure sensitive.^71,72  This significant size-dependent reactivity was confirmed with unsupported gold nanoparticles, showing optimum performance for particles with diameters <5 nm. Nevertheless, unsupported bulk Au itself was also reported to catalyze the aerobic oxidation of π-activated alcohols, such as BA and CA,⁷³  indicating that the favorable interaction between the gold surface and the π-system of the aromatic ring is able to enhance the overall efficiency of the active site even in the presence of bulk metal. In fact, the authors found that the π-activation for the –CH₂OH group by the phenyl group in benzyl alcohol was critical for oxidation using bulk Au.

Micro- and mesoporous oxide architectures with high surface area and regular channels have been widely used as a framework for metals, limiting the agglomeration of nanoparticles and relative deactivation. Parlett and co-workers^74–76  recently reported that Pd and Pt dispersed over mesoporous SiO₂ are very active in the oxidation of crotyl alcohol and cinnamyl alcohol. Moreover, they demonstrated that extremely low palladium loadings generate atomically dispersed Pd²⁺ surface species that impart unusual activity in the oxidation of allylic alcohols. The same group demonstrated the usefulness of hierarchically ordered nanoporous Pd/SBA-15 in the oxidation of sterically hindered allylic alcohols – such as farnesol and phytol – to their aldehydes.⁷⁵  The results data indicated that, in order to obtain Pd catalysts that are efficient for the aerobic oxidation of these large molecules, support materials capable of stabilizing high amounts of PdO nanoclusters (<2 nm) but with pores large enough to minimize mass-transport limitations are required.

The rate and selectivity of alcohol oxidation depend strongly on the reaction conditions and the positive effects of a homogeneous added base (mainly NaOH, KOH and K₂CO₃) on the performance of metal-catalyzed reactions were extensively reported.⁶⁶  It was hypothesized that the base aids alcohol dehydrogenation by H abstraction, thus overcoming the rate-limiting step in the oxidation, and helps in desorbing carboxylic acid formed during the reaction, thus avoiding poisoning of the catalyst. Nevertheless, the addition of homogeneous bases to the reaction solution may be negative from environmental and economic standpoints, and a significant amount of work has recently been devoted to research on alternative methods to their use.

As an alternative to adding a homogeneous base, different groups have investigated the use of solid bases (mainly MgO, but also more unusual materials such as NiO) and hydrotalcite materials as supports for metal catalysts.^77,78  Specifically, Ebitani and co-workers⁷⁸  demonstrated that platinum/gold alloy nanoparticles supported over hydrotalcites were truly effective catalysts for the selective aerobic oxidation of glycerol and 1,2-propanediol in base-free aqueous solution when using molecular oxygen at room temperature and atmospheric pressure. The high activity and selectivity of these catalysts were explained in terms of alterations of geometric and electronic states of the catalytically active surface Pt sites by Au atoms and starch ligands used for nanoparticle synthesis.

On the other hand, it appears that, using basic supports, the acid formed in the oxidation reaction can either be absorbed on the solid surface or react with the support, thus leading to catalyst deactivation or leaching of the material into the reaction medium. Accordingly, basic supports seem to serve more as a stoichiometric replacement for the homogeneous base rather than as catalytic materials.

A major topic in the aerobic oxidation of alcohols is the performance of bimetallic catalysts. The alloying of different metals has indeed proven to have the potential for preventing catalyst deactivation, enhancing reaction rates and improving product selectivity.⁷⁹ 

As an example, the preparation of Au/Pd- and Au/Pt-supported materials and their use in the oxidation of alcohols has attracted high levels of research.^80,81  Supported Au/Pd nanoparticles proved to be highly effective as catalysts for the solvent-free oxidation of BA.⁸²  Nevertheless, in some cases, the coproduction of large amounts of toluene was observed, due to the presence of a disproportionation reaction of benzyl alcohol.⁷⁰  This latter reaction seems to be especially promoted by Pd. The use of supports such as MgO or ZnO was reported to stop toluene formation completely, while the thermal treatment of prepared catalysts at different temperatures led to significant changes in the ratio between main products and by-products.⁸³ 

Recently, in order to elucidate the structure–activity relationships in the reaction of BA oxidation, Hutchings and co-workers reported the catalytic performance of Pt/Au and Pt/Pd nanoparticles supported over TiO₂ and active carbon using tert-butyl hydroperoxide (TBHP) as the oxidant. The results demonstrated that when Au/Pd catalysts were used, a notable amount of toluene was identified,⁸⁴  whereas when Pt was used instead of Pd in the alloy, toluene was not formed and the main products were benzaldehyde and molecules deriving from aldehyde.⁸⁵ 

As alternatives to noble metals, low-cost metals and metal oxides are currently being explored as catalysts for the reaction of alcohol oxidation.^68,86 

The use of a manganese-doped cobalt mixed oxide catalyst prepared by a solvothermal method was proposed in the oxidation of vanillyl alcohol to vanillin without using a base.⁸⁷  Three different types of metal oxides were observed in the prepared catalysts, which could be identified as Co₃O₄, Mn₃O₄ and CoMn₂O₄. Among these, the tetragonal phase of CoMn₂O₄ was found to be the most active and selective for vanillyl alcohol oxidation. The successful recycling of the catalyst was also achieved in this oxidation reaction.

A recent study by Zhu et al.,⁶⁸  using various metal oxides supported on activated carbon (AC), indicated that cobalt and nickel oxides are the most promising catalysts for the aerobic oxidation of benzyl alcohol, whereas manganese, iron and copper oxides showed lower conversion and selectivity. The Co₃O₄/AC catalyst showed high activity under mild conditions in the absence of an added base and the activity was ascribed to the synergistic effect of Co₃O₄ and AC. The proposed reaction mechanism indicated that Co₃O₄ is responsible for the alcohol dehydrogenation step, whereas carbon provides sites for molecular oxygen activation. However, a high load of cobalt oxide over the support was necessary to obtain significant activity and the catalyst could be reused only after thermal treatment at high temperature (350 °C).

The selective oxidation of oxygenate compounds derived from renewable feedstocks has been extensively explored over the past 10 years.^65,66,88  The use of metals, mainly Au-, Pd- and Pt-supported catalysts, for the liquid-phase oxidation of a variety of molecules of interest in biomass conversion (polyols, carbohydrates, glycerol and furans) has attracted a great deal of attention from researchers. The main example of this class of reactions is glycerol oxidation.^88–91  Glycerol is a major by-product of biodiesel synthesis and its oxidation to high-value chemicals – such as tartronic acid, glyceric acid and dihydroxyacetone (Scheme 1.18) – can help biodiesel economics become more competitive.

The use of gold catalysts for the selective oxidation of glycerol has increased significantly over the past decade.^92,93  Davis and co-workers demonstrated that Au was more active than Pd and Pt with the use of high base concentration, whereas the activity of bimetallic Pd/Au systems was significantly lower than that of monometallic Au but led to greater formation of glyceric acid.⁹⁴  It was also demonstrated that hydrogen peroxide was formed during glycerol oxidation and its formation was associated with an increased presence of base in solution;⁹⁵  the H₂O₂ formed can cause carbon–carbon bond cleavage and increase the formation of by-products during oxidation reactions.

The selective oxidation of glycerol by bimetallic Au/Pd and Au/Pt catalysts supported over MgO at ambient temperature and under base-free conditions was reported by Hutchings and co-workers.⁹⁶  The reactivity at low temperature under base-free conditions highlighted the activity of PtAu/MgO materials. In particular, the alloying of Au with Pt leads to the enhancement of both glycerol conversion and selectivity towards C₃ products compared with Pd.

One of the most important sources of biomass is sugars, which are widely available and easily transformed. The homogeneous dehydration of glucose and/or fructose leads to the formation of 5-hydroxymethyl-2-furfural (HMF), which is a key precursor for the synthesis of chemicals that have applications in the polymer and pharmaceutical industries.^97–99  In particular, HMF can be oxidized to 2,5-furandicarboxylic acid (FDCA), which has recently been proposed as a possible surrogate for terephthalic acid,¹⁰⁰  the monomer used for the production of terephthalate plastics.

The synthesis of FDCA from HMF has been widely studied in the last two decades by using different catalysts and reaction conditions. Scheme 1.19 shows the general HMF oxidation pattern. FDCA is generally produced in two stages: the aldehyde functional group is first oxidized to a carboxylic acid, producing 5-hydroxymethyl-2-furancarboxylic acid (HMFCA); then, typically, the oxidation of the hydroxymethyl group produces FDCA through 5-formyl-2-furancarboxylic acid (FFCA) intermediates. Furthermore, sometimes the formation of 2,5-diformylfuran (DFF) has been observed, mainly in the absence of an added base.

Recent representative results reported in the literature are summarized in Table 1.1.

Supported Au nanoparticles have been found to be very active catalysts for 2,5-furandicarboxylic acid synthesis and many researchers have focused their attention on searching for the best supports and reaction conditions for improving the product yield.^101–106  In particular, Davis et al.¹⁰⁴  reported that gold-based materials were more active than other metals in the first step of the HMF oxidation, leading to HMFCA very quickly, even though they showed less activity for the subsequent conversion of HFCA to FDCA. The mechanism of HMF oxidation over Au and Pt catalysts in the presence of high amounts of NaOH was recently investigated through the use of isotopically labeled dioxygen and water.¹⁰⁵  The source of oxygen insertion was shown to be water rather than oxygen in all cases. It was suggested that the role of O₂ was that of an electron scavenger, closing the catalytic cycle and allowing the reaction to proceed. However, generally, process efficiency and, in particular, catalyst stability over gold-based samples proved to be rather low.

As also reported for other alcohols, the addition of a second metal to gold was shown to improve strongly the catalytic activity and stability in the reaction of HMF oxidation. In particular, Au–Cu-supported nanoparticles have been shown to produce active and stable catalysts for this reaction.^107,108  A strong synergistic effect was evident with the addition of Cu to Au up to a Cu:Au ratio of 1:1, especially in terms of sample stability and resistance to poisoning. Au–Cu alloy nanoparticles were considerably more active and selective than their monometallic counterparts. Moreover, reusability tests showed that the Au–Cu-based catalysts were significantly more stable than their monometallic counterparts.

Villa et al.¹⁰⁹  demonstrated that the modification of Au-based catalysts with Pt or Pd metal also produced stable and recyclable catalysts. In particular, they reported that bimetallic Au₈Pd₂ species supported over active carbon – where Au and Pd metal are present in an 8:2 molar ratio – have the highest activity and stability for the production of FDCA.

Another solution to the problem of catalyst durability was the addition of bismuth to Pt-containing catalysts.¹¹⁰  In this case, the oxidation of HMF proceeded via the HMFCA and DFF intermediates; both of which were very reactive and rapidly oxidized to 5-formylfurancarboxylic acid (FFCA). The ex situ or in situ addition of a Bi promoter prevented the deactivation of the Pt catalysts and accelerated the reaction. The highest activity was observed for a Bi/Pt molar ratio of approximately 0.2.

Similar results were obtained by Villa et al.¹¹¹  when studying the modification of Au–Pd catalysts with bismuth and using the prepared systems in alcohol oxidation. Bi-containing materials were demonstrated to increase selectivity by suppressing parallel reactions in both benzyl alcohol and glycerol oxidation. However, the selectivity of the reactions notably varied only when Bi was deposited on the surface of metal nanoparticles.

One of the greatest challenges in liquid-phase oxidation catalysis is the development of clean technologies that can operate in water; many of the studies reported so far used this solvent, even though reactants and products in alcohol oxidation are often insoluble in water, so other alternatives to standard organic solvents have also been proposed, such as ionic liquids^112,113  and supercritical fluids.^114–116 

The properties of supercritical carbon dioxide (scCO₂) are a combination of those associated with gases or liquids¹¹⁷  and are particularly useful in the reactions involving gaseous reagents such as hydrogenation with H₂ and oxidation with O₂. Moreover, scCO₂ is totally non-flammable and its properties can be manipulated by varying the pressure applied.

The selective aerobic oxidation of alcohols has been studied in depth in scCO₂ using both batch and continuous-flow reactors.^114,118  The products usually observed in the oxidation of primary alcohols with metal catalysts and their formation routes are depicted in Scheme 1.20.

Since scCO₂ can dry wet material by eliminating the water formed during alcohol oxidation, its application is convenient for achieving high selectivity to aldehyde, while suppressing the formation of carboxylic acid via the favored hydration of aldehyde.¹¹⁹ 

Apart from reaction selectivity, a strong dependence of the reaction rate on pressure has also been found in some cases where CO₂ has been used as the solvent. As an example, Caravati et al.¹²⁰  demonstrated that the conversion of benzyl alcohol to benzaldehyde in CO₂ increased from 25 to 75% when the pressure was increased from 140 to 150 bar. Moreover, the same group¹²¹  showed that, depending on the pressure, substrate and products are distributed differently in the organic and supercritical phases, thus affecting both the reaction rate and the selectivity (Figure 1.2). Biphasic conditions at pressures close to the dew point resulted in the highest reaction rate, with formation of significant amounts of toluene (25%) as a side product, whereas working in a single phase led to the formation of over-oxidation products as the dominant side products.

Over recent decades, the study of metal nanoparticles – generally so-called when their size is between 1 and 10 nm – with high specific catalytic activity has been widespread in synthetic organic chemistry.^122–124  Owing to their particular state of matter, between homogeneous and heterogeneous, these species are often called ‘semi-heterogeneous’ catalysts. In general, the advantageous characteristics of nanoparticles are (i) high surface-to-volume ratios, providing a considerable number of active sites per unit area compared with their heterogeneous counterparts,¹²⁵  (ii) high zeta potential, preventing the aggregation of nanoparticles in solution¹²⁶  and (iii) the possibility of separation and recycle, making them cost-effective and minimizing the chance of contaminating the catalyst with the product.¹²⁷ 

Recently, nanometals and nanoclusters have been widely applied in some important reactions,¹²⁸  such as the carbon–carbon coupling,¹²⁹  carbon–heteroatom bond formation¹³⁰  and hydrogenation.¹³¹ 

A recent review by Garcia and co-workers¹³²  suggested that the intrinsic activity of unsupported gold nanoparticles in some of the typical reactions generally promoted by supported nanoparticles, such as aerobic alcohol oxidation, is comparable to or even higher than those of conventional supported materials. As an example, monodisperse gold and palladium nanoparticles, stabilized by polyvinylpyrrolidone (PVP), were tested in the oxidation of benzyl alcohols in water.¹³³  In these tests, Au nanoparticles proved to be more active than Pd nanoparticles of similar size (about 1.5 nm). In addition, in kinetic experiments, the rate-determining step for BA oxidation was reported to involve hydrogen abstraction by a superoxo-like molecular oxygen (O₂^•−) which was adsorbed on the catalyst. This specific species can only be formed over small metal clusters, which might explain the size-related catalytic activity in alcohol oxidation that was observed in gold-based samples.

Dumeignil and co-workers¹³⁴  recently proposed a complex reaction scheme for the liquid-phase oxidation of glycerol using a quasi-homogeneous solution of Au nanoparticles. The highest conversion of glycerol obtained with this system was 100% after 3 h of reaction at 100 °C and 6 bar oxygen pressure, and the main products formed were glyceric, glycolic, formic, tartronic and oxalic acid with selectivities of 28, 36, 25, 9 and 2%, respectively. The mechanism reported indicated that the direct glycerol oxidation was facilitated in the presence of Au nanoparticles, whereas high temperatures and strongly basic conditions facilitated oxidative cleavage and straight hydrolytic transformations, such as retro-aldol, dicarbonyl cleavage, oxidative cleavage with carbon dioxide evolution and Cannizzaro cross-reactions.

So far, the role of the ligand generally used to stabilize nanometals from grain growth and agglomeration during catalytic tests has not been sufficiently investigated. In this regard, it has been commonly assumed that the ligand plays a negative role, by significantly decreasing the catalytic activity of nanoparticles.¹³⁵  Nevertheless, using PVP, it was observed that the interaction of this polymer with metal nanocrystals is accompanied by charge transfer from PVP to the nanometal.¹³⁶  Thus, in some cases, this interaction can modify the structure of metal colloids in ways that are sometimes beneficial to their catalytic performance.¹³⁷ 

Also with nanoparticles, owing to the limited reserves of noble metals, one of the most interesting challenges is that of reducing their content in the active phase. Both intermetallic noble–non-noble alloys and non-noble metals have been demonstrated to be effective in reducing the use of noble metals for catalytic applications. As with the case of supported systems, in many cases the alloyed nanosystems not only combined the properties of monometallic nanoparticles, but also showed a significant improvement because of synergistic effects and different compositions.⁸¹ 

Scott and co-workers¹³⁸  studied the oxidation of α,β-unsaturated alcohols in water and an ionic liquid (tetraalkylphosphonium chloride) catalyzed by monometallic and bimetallic Pd and Au nanoparticles. In water, bimetallic Au–Pd nanoparticles were demonstrated to oxidize most of the unsaturated alcohols; however, the particle size growth due to Ostwald ripening was problematic. Conversely, the monometallic Pd system showed significant catalytic activity when using tetraalkylphosphonium chloride as a solvent, likely due to the easy oxidation of Pd in the high-chloride environment, whereas gold was inactive.

If heterometals with magnetic properties are alloyed into active phases, it is possible to overcome the drawback of nanoparticle separation and reuse.¹³⁹  Thus, magnetically separable nanocatalysts may have potential applications in catalysis.

Definite supports can also be chosen to enhance the recyclability of nanoparticles. Microgels, for example, have been used for this purpose.^140,141  For instance, Prati and co-workers synthesized microgel-stabilized Au nanoparticles by using tailor-made soluble cross-linked polymers as exotemplates and stabilizers.¹⁴¹  The resulting stabilized system could be conveniently isolated by precipitation, stored in the solid state and re-dispersed in polar organic solvents and water. The prepared catalytic system exhibited remarkable activity in the oxidation of benzylic acid and polyols under mild conditions.

Looking at both the examples presented and the large number of papers on catalysis by nanoparticles which have recently appeared in the literature, we can conclude that significantly increased research in the area of unsupported nanoparticles may be expected in the coming years. In fact, metal colloids can actually be prepared following some accurate and reliable procedures,¹⁴²  thus ensuring the synthesis of materials with controlled characteristics and well-defined crystallographic planes, very close to theoretical models. Hence these tuned materials could be used to validate the preferred reaction for specific plane orientation and also for testing specific reaction mechanisms.

The field of microwave (MW)-assisted chemistry is relatively young. Nevertheless, since the first published reports on the use of MW irradiation to carry out chemical reaction in 1986,^143,144  the heating of the chemical reactions by MW energy has been an increasingly popular subject and a large number of papers have been published in this field over the past 20 years (Figure 1.3).

In many of the published studies, MW heating strongly decreased processing times, increased product yields and increased product purity, compared with conventional heating methods.^145–149  The nature of the MW enhancement is usually attributed to several specific thermal effects that cannot be emulated by conventional heating methods, such as the rapid heating rate, the prevention of thermal wall effects and the selective heating of particular reaction components and/or intermediates.

More recently, the advantages of this empowering technology have been exploited in the fields of nanomaterial synthesis^150–153  and catalysis.¹⁵⁴ 

As an example, MW effects in heterogeneous catalysis were investigated in the dehydrogenation reaction of decalin and tetralin.^155,156  The use of MW heating proved both to improve the reagent conversion and to lower the deactivation rate of the catalyst. An observed beneficial effect of MW use was the large temperature gradient between the catalyst and surrounding species (direction of heat transfer reversed compared with the thermal mode). This led to the acceleration of mass desorption and species transport in the system, reduction of coke deposition and enhancement of tetralin dehydrogenation. Nevertheless, evidence of the MW effect was only observed in reactions controlled by mass transfer as the rate-limiting step.

Supported iron oxide nanoparticles on aluminosilicate catalysts were found to be efficient and easily recoverable materials in the aqueous selective oxidation of alcohols to their corresponding carbonyl compounds under both conventional and microwave heating.¹⁵⁷  The use of catalysis in conjunction with microwave heating resulted in dramatic reductions in reaction time, which decreased from hours to minutes. Similar results were obtained by García-Martínez and co-workers when using iron oxide nanoparticles (0.5–1.2 wt%) on MCM-41 type silica materials.¹⁵⁸ 

Photocatalysis is a branch of chemistry that exploits light radiation to overcome the energy barriers of chemical reactions.¹⁵⁹  Solar light is a renewable source of energy but only in the last century has it been analyzed as a potential motor for chemistry. Photochemical processes between light and matter are now being studied to become both supplementary and complementary to traditional reactions. So far, the most studied applications for photocatalysis have been the destruction of pollutants in water^160–162  and water splitting.¹⁶³ 

Nevertheless, photocatalysis has recently been used for the oxidation reactions of both aliphatic and aromatic alcohols and a review on the transformation of alcohols by heterogeneous photocatalysts was published fairly recently.¹⁶⁴ 

Pristine and doped titania have been mainly used as photocatalysts, owing to their reliability, stability under irradiation and low cost, although different semiconductor and insulator solids have also been used. Recently, Augugliaro and co-workers¹⁶⁵  investigated the UV photo-oxidation of piperonyl alcohol in water using a TiO₂ suspension. All the TiO₂ samples, prepared by the hydrolysis of TiCl₄ or from TiOSO₄ precursor – less crystalline and more hydroxylated than commercial titania – exhibited higher selectivity, but their reaction rate was higher in the presence of commercial Degussa P25. This behavior was in accordance with previous results obtained for the selective oxidation of other alcohols to the corresponding aldehydes.^166,167  Other products formed, in addition to piperonal, were carbonic anhydride and 1,3-bis[3,4-(methylenedioxy)benzyl] ether (Scheme 1.21); traces of this last compound were found only starting from the highest concentration of alcohol.

The use of heterogeneous photocatalysis for selective chemical transformations of biomass-derived compounds was reviewed recently.¹⁶⁸  The catalytic selective photo-oxidation of biomass was reported to provide various platform molecules such as levulinic, 2,5-furandicarboxylic, succinic, gluconic and glucaric acids.¹⁶⁹  In general, the observed oxidation of alcohols is highly dependent on the class of molecules. The conversion of primary alcohols was usually low but with high selectivity. With regard to the reaction mechanism, it has been suggested that the first step corresponds to the interaction of a surface hole with the hydroxyl group of the alcohol, thus forming metal–oxo species with proton removal. This step becomes easier with carbon branching and as the chain length increases.

The efficiency of TiO₂ catalysts in the selective photocatalytic oxidation of glucose has also been reported recently,¹⁷⁰  and the reaction was found to be very selective towards glucaric and gluconic acids. Similarly, the mechanism of the selective photooxidation of glycerol over TiO₂ was studied.¹⁷¹  In particular, glycerol was used as a probe molecule to study the mechanism on the catalyst surface, because the determination of the produced intermediates made it possible to discriminate between direct electron transfer and a radical-mediated oxidation mechanism.

A significant improvement in the photoactivity of nanooxides, such as TiO₂, by the use of MW irradiation was described by Serpone and co-workers.^172–174  In particular, they reported that, even though the idea of irradiating TiO₂ with microwaves may appear strange – since the MW photon energy (1×10⁻⁵ eV) is several orders of magnitude lower than the bandgap energy (3.0–3.2 eV) of TiO₂ – thermal and non-thermal factors can contribute significantly to the enhancement of a TiO₂ photo-assisted reaction, because MW heating may affect both crystalline and surface structures of the metal oxide. In fact, when studying the impact of MW iradiation on the degradation of Rhodamine B (RhB) dye and 1,4-dioxane, the latter demonstrated an important increase in the molecule degradation rate using MW-assisted photo-oxidation.¹⁷²  When using this procedure, in fact, the increase in the hydrophobic nature of titania under MW irradiation was reported to facilitate the adsorption of RhB through the aromatic rings with the aid of the three oxygen atoms in RhB. In other words, RhB lies flat on the particle surface. A similar MW effect was observed in the photo-degradation of many organic pollutants in aqueous media. In these studies, the possible advantages of MW heating in obtaining photo-degradations and photo-mineralizations of various organic pollutants was described; nevertheless, the reported research seems to indicate that the coupling of MW irradiation with a UV light source may lead to interesting results for partial oxidation reactions also.

In the field of metal-catalyzed aerobic alcohol oxidations, great efforts have been made over the past decade in the development of processes capable of meeting the ideal requirements for ‘green chemistry’: (i) good yields, (ii) high selectivity, (iii) use of green solvents (such as water) and (iv) atom economy. Many steps forward have been achieved within the last few years. In particular, with regard to homogeneous catalysis, the case study of Stahl's Cu/nitroxide system is a good example of the crucial points to be followed in the rational design of new homogeneous catalysts with the aim of broadening the substrate scope and improving reaction conditions. The choice of the ligand and co-catalyst proved crucial, and in-depth mechanistic investigations made it possible to shed more light on the properties of the catalyst to be tailored. Several mono- to tetradentate N,O- or carbene-based ligands, recently used for the preparation of Cu, Pd, V and Fe catalysts, proved that, by varying the structure of the ligands, better selectivity and the possibility of working with green solvents such as water can be tailored by design. Great effort has also been devoted to the development of one-pot syntheses toward the preparation of fine chemicals. Elegant tandem approaches have been reported for the direct synthesis of heterocyclics, imines and nitriles from alcohols and a nitrogen source.

New heterogeneous catalysts for the aerobic oxidation of alcohols have attracted much attention in recent years. Monometallic and bimetallic transition metal-based systems have been successfully applied to the aerobic oxidation of alcohols to the corresponding carbonyl compounds using O₂; several of them exhibited excellent performance. In particular, the use of gold-based bimetallic alloys led to significant results for the oxidation of a variety of molecules, especially significant in the production of chemicals from biomass sources. Tuning the product selectivity to acid or aldehyde may be most easily achieved by selecting the solvent. Water facilitates the formation of acid, while unusual solvents such as scCO₂ may facilitate high selectivity to aldehyde.

Nanocatalysis is the subject of intense research, and an appreciable increase in the achievement of results in this area may be expected in the coming years. The synthesis of tuned nanomaterials with controlled chemical–physical properties may in fact be used to validate theoretical calculations and to test specific reaction mechanisms while avoiding the interference of support materials on the active phase.

The use of photochemistry under mild conditions to convert alcohols selectively to chemicals is an innovative approach. In the near future, integrated systems of MW and photo-catalyst systems may be available; ideal photo-catalysts for commercial applications, however, should work under solar light irradiation in aqueous solution and only very few studies on sunlight use have been reported in the literature.

Although recent advances have shed more light on the mechanisms of the aerobic oxidation of alcohol and broadened the scope of substrates, selectivity and synthetically significant compounds, there is still plenty of room for further improvements of catalyst performance in the exploration of the potential usefulness of this system in industrial processes.