3.1 Photocatalysis by metal chlorides

In 90s we have described a new photocatalytic method for the transformation of alkanes and arylalkanes into corresponding hydroperoxides. Various metal chlorides were used as catalysts, but iron(III) chloride has been found to be the most efficient photocatalyst of alkane oxidation with atmospheric oxygen [14–22]. Halogenides of other transition metals CuCl₂ [18, 21, 23, 24], AuCl₄^– [18, 21, 25, 26], PtCl₆^2– [18, 26, 27], PtBr₆^2–, RhCl₃, RuCl₃ [17] and CrCl₃ + PhCH₂NEt₃Cl [28] also efficiently catalyse the aerobic oxygenation of alkanes in acetonitrile, methylene chloride or acetic acid under light irradiation. Methanol and formaldehyde were formed upon the slow bubbling of methane and air through a solution of HAuCl₄ in MeCN under irradiation [25].

The proposed mechanism for the oxidation catalysed by iron(III) chloride includes as the first step the photo-excitation of the metal-containing species to stimulate homolysis of the Fe–Cl bond [22]. The chlorine radical attacks further the alkane. The formed iron(II) derivative can be oxidized either by molecular oxygen or the alkylperoxo radical.

Bromide complexes are also efficient in the photooxidation; however, in these cases the oxygenation of only alkylbenzenes (and not of alkanes) can be carried out. This can be due to lower reactivity of the bromine radical, which plays the role of an active species in this reaction. Mechanisms of the photooxygenation reaction in the cases of other than iron metal seem to be different from that postulated for the FeCl₃-catalysed process [22]. Low-valent metal-containing species are apparently involved in the oxidation. It is interesting that the aerobic cyclohexane photooxidation in the presence of a catalytic system CrCl₃–PhCH₂NEt₃Cl in MeCN produces not the corresponding cyclohexyl hydroperoxide but gives the ketone as a main product and only a small amount of the alcohol [28].

3.2 Photocatalysis by oxo complexes

In our earlier works, we demonstrated that the oxidation of alkanes and aromatic alkyl-substituted compounds by oxo derivatives of chromium(VI) is greatly accelerated by light irradiation [29–33]. Later we found that oxo compounds such as K₂Cr₂O₇ in the two-phase solvent water-1,2-dichloroethane [34], CrO₃ [35], complexes (n-Bu₄N)₂Cr₂O₇, (n-Bu₄N)₂Cr₃O₁₀ and (n-Bu₄N)Cr₄O₁₃ [36], and UO₂Cl₂ [37] catalyse the photooxygenation of alkanes. Moreover, catalytic amounts of heteropolyoxometalates in methylene chloride, acetic acid, alcohols, acetone, acetonitrile [38, 39] transform alkanes and arylalkanes into the corresponding alkyl hydroperoxides as well as ketones and alcohols. Photooxygenation of alkanes catalysed by molybdenum or tungsten carbonyls begins apparently from the transformation of the carbonyl into an active oxo species [40, 41]. Some other chromium and vanadium complexes have been reported to be catalysts of alkane photooxidation [42–46]. The mechanism of aerobic alkane photooxidation catalysed by metal oxo complexes includes the formation of a photo-excited species, which is capable of abstracting a hydrogen atom from an alkane.

3.3 Photocatalysis by other complexes

The photooxidation of alkanes in acetonitrile occurs also in the presence of a catalytic amount of cyclopentadienyliron(II) complexes and bis(arene)iron(II) [47, 48]. The irradiation of an aqueous cyclohexane emulsion in the presence of an iron(III) salt, e.g. Fe(ClO₄)₃, gives rise [49] also to the formation of cyclohexanone instead of its mixture with cyclohexyl hydroperoxide and cyclohexanol. Palladium trifluoroacetate oxidizes alkanes under light irradiation [50].

3.4 Aerobic photooxidations catalysed by the ‘quinone-copper acetate’ system

Under the irradiation with visible light, an acetonitrile solution of an alkane and catalytic amounts of quinone and copper(II) acetate produces almost pure alkyl hydroperoxide, which decomposes only very slowly under these conditions [11, 51]. The first step of the reaction is a hydrogen atom abstraction from the alkane, RH, by a photo-excited quinone species to generate the alkyl radical, R^•, and semiquinone. The former is rapidly transformed into ROO^• and then into alkyl hydroperoxide, while the latter is re-oxidized by Cu(II) into the initial quinone.

4.1 Catalysis by metaloporphyrins

Porphyrin complexes of some transition metals are used as models of heme monooxygenases. The porphyrin ring can play the role of an electron donor owing to its ability to generate the radical cation and thus become an active participant of the catalytic process. If molecular oxygen is the oxidant in model reactions, a reducing agent is required whose role can be played, for example, by metallic zinc, thiosalicylic acid or molecular hydrogen. We employed in our investigations ferrocene and benzylferrocene as the reductant and tetraphenylporphyrinate complexes of cobalt(II) or iron(III) [52]. Alkane oxidation in the presence of air and an electron source occurs at normal temperature and pressure. In the cyclohexane oxidation, cobalt-containing catalyst turned out to be more efficient than iron porphyrin, and the product yield was higher when benzylferrocene was used instead of ferrocene.

4.2 Catalysis by complexes of vanadium, gold and manganese

Metal porphyrinates can be replaced in biomimetic studies by simple salts of transition metals. We have found that FeCl₃, CuCl₂ and NaAuCl₄ induce aerobic oxygenation of benzene, ethylbenzene, styrene, cyclohexane and n-hexane in aqueous acetonitrile if ascorbic acid is added to the solution [53]. However, unfortunately turnover numbers (moles of products per one mole of the catalyst) did not exceed 3. When d-glucose was used instead of ascorbic acid, only ethylbenzene have been oxygenated, CuCl₂ exhibited the highest activity.

Vanadium is known to play the important role in biology. Some complexes have been used as models of natural vanadium-containing compounds (see, for example, [54]). Recently we demonstrated [55] that vanadium complexes (particularly vanadate anion) catalyse aerobic hydroxylation of benzene to phenol in acetonitrile in the presence of solid ascorbic acid and with obligatory participation of pyridine, pyrazine-2-carboxylic acid and acetic acid as mediators of proton and electron transfer. If some water is added to the system containing ascorbic acid, this compound is dissolved in aqueous acetonitrile and no hydroxylation occurs. The oxidation of toluene under the same conditions gave a mixture of isomeric cresols with the ratio o:m:p = 60:16:24. Naphthalene gave isomeric naphthols (α:β=4:1). Ascorbic acid can be replaced with zinc powder. The zinc-based system hydroxylates not only benzene and aromatic ring and methyl group in toluene (o:m:p = 47:28:25) but also C–H bonds in cyclohexane with total turnover number being 78. A mechanism of the formation of hydroxyl radicals by these systems has been proposed (Fig. 1). Initial vanadium(V) species, conventionally depicted in the scheme as 1, is reduced to a catalytically active V(IV) form 2 by ascorbic acid or Zn⁰. The latter species adds molecular oxygen and after reduction is converted to a hydroperoxy V(IV) species (5). A homolytic splitting O–O bond in this species gives rise to more stable oxo derivative of V(V), 6, and hydroxyl radical. Finally, step 6 leads to the initial catalytically active species 1. In this sequence of stages, PCA can facilitate proton transfer, for example intermolecular transfer between two HO groups or between proton donors from the reaction media and oxo or hydroxy groups at the vanadium ion. Protonated pyridine apparently plays the role of a hydrogen atom mediator and is a model of NADH. Reduction of V(V) by NADH in biological systems is known [56, 57]. Thus we can conclude that these systems mimic generation of hydroxyl radicals in certain vanadium-dependent biological processes.

The oxidation of cyclooctane by air at room temperature catalysed by NaAuCl₄ in the presence of Zn/CH₃COOH as a reducing agent and methylviologen as electron-transfer agent gave cyclooctanol (TON = 10) [58]. A binuclear Mn(IV) complex with the 1,4,7-trimethyl-1,4,7-triazacyclononane macrocyclic ligand (compound 21; see below) initiates oxidation of cyclohexanecarboxaldehyde with atmospheric oxygen in acetonitrile under heating resulting in the formation of cyclohexanecarboxylic acid and considerable amounts of oxidative decarboxylation products, i.e., cyclohexane, cyclohexanol and cyclohexanone [59]. In the presence of cyclooctane, the reaction gives rise also to the formation of cyclooctanol and cyclooctanone.

4.3 Dioxygenase-like vanadium-catalysed splitting C–C bonds

Brégeault and co-workers have shown that vanadium complexes catalyse aerobic oxidation of ketones with splitting C-C bonds; particularly, 2-hydroxycyclohexanone can be easily oxidized to adipic acid [60, 61]. Very recently, we used the mononuclear anionic dioxo vanadium (V) species, [{Ph₃SiO}₂VO₂]^–, and the dinuclear complex anion, [{Ph₂SiO₂VO₂}₂]^2–, as well as simple vanadium derivative, n-Bu₄NVO₃, VOSO₄·5 H₂O, VO(acac)₂, H₆PMo₉V₃O₄₀ as catalysts for the aerobic C–C-bond cleavage in 2-hydroxycyclohexanone and of 2-methylcyclohexanone [62]. On the basis of the obtained data, a mechanism has been proposed, which is depicted in Fig. 2 for the case of C–C-bond cleavage in 2-hydroxycyclohexane. This scheme presents a formally closed catalytic cycle, although we realise that in reality some other steps take place and the equilibria are more complex. The reaction can begin from the formation of catalytically active oxovanadium(V) species 6, which is depicted as [VO₂]⁺X^–. Certainly this species contains some additional ligands such as coordinated water from the organic solvent. Species 6 can be coordinated to the substrate molecule via its hydroxyl oxygen to produce complex 7. Proton transfer from the carbon atom to the oxo group leads to the formation of the enol form (8). Naturally, this proton transfer does not occur in an intramolecular way, as it is schematically shown as Step 2, but via deprotonation and protonation, with participation of the solvent or water (which was present in relatively small concentrations in all reaction solutions). Step 3 is a single electron transfer from the electron-rich organic moiety to the V(V)-oxo part of the complex to produce species 9, which contains the n-coordinated to V(IV) organic part of the complex. There is an unpaired electron on the organic ligand, and one of the mesomeric forms of 9 can be a carbon-centred radical. In the presence of molecular oxygen species 9 will react rapidly with O₂. Indeed, it is well known [8] that carbon-centred radicals add to the oxygen molecule in a very fast reaction:

A similar mechanism has been proposed previously for the oxidative C–C bond splitting in coordinated to palladium(II) acetylacetonate ligand to afford acetate ligand [8, 63]. In that case, the reaction proceeded smoothly at room temperature under irradiation by visible light. Another ligand, the coordinated to Pd(II) ortho-metalated azobenzene played a role of an ‘antenna’, absorbing the light energy necessary for the electron transfer from the acac ligand to the palladium centre. It should be noted that such a type mechanism is relative to the mechanism of C–C bond splitting in substituted phenols and catechols under the action of O₂, catalysed by enzymes non-heme iron dioxygenases (see, for example, [64–67]). Thus oxidative systems based on vanadium complexes can be considered as biomimetic models of dioxygenases.

5.1 The ‘O₂–H₂O₂–vanadium complex–pyrazine-2-carboxylic acid’ reagent

Any soluble vanadium derivative [vanadate anion in the form n-Bu₄NVO₃, or VOSO₄, VCl₃, VO(acac)₂] can be used as a catalyst in combination with pyrazine-2-carboxylic acid as co-catalyst for the oxidations with hydrogen peroxide in acetonitrile solution [12, 68–83]. At low temperatures, the predominant product of the alkane oxidation is the corresponding alkyl hydroperoxide (alcohols and ketones or aldehydes are formed simultaneously in smaller amounts). This alkyl hydroperoxide then slowly decomposes to produce the corresponding ketone and alcohol. The amounts of alkyl hydroperoxide, alkanol and alkanone were estimated by comparing the data of chromatographic analysis of the solution before and after reduction with triphenylphosphine (see above), as well as by direct measure of the intensities of the peaks corresponding to ROOH. Atmospheric oxygen takes part in this reaction; in the absence of air, the oxygenation reaction does not proceed. Thus it may be concluded that in alkane oxidation, hydrogen peroxide plays the role of a promoter, while atmospheric oxygen is the true oxidant. The oxidation of n-heptane by the reagent under consideration exhibits low selectivity, C(1):C(2):C(3):C(4) ≈ 1:4:4:4. This parameter is close to that found for the oxidation of n-heptane by H₂O₂ in MeCN under UV irradiation (1.0:3.4:3.2:3.0). The selectivities of the reactions with branched alkanes (2- and 3-methylhexane, cis- and trans-decalin) are also very similar to those observed with hydroxylation of the alkanes with hydrogen peroxide under UV irradiation. Methane, ethane, propane, n-butane and isobutane can be also readily oxidized in acetonitrile by the same reagent. Alcohols, aldehydes or ketones and carboxylic acids are obtained with high total turnover numbers (at 75 °C after 4 h: 420 for methane and 2130 for ethane) and H₂O₂ efficiency in addition to the primary oxidation products (alkyl hydroperoxides). Methane can also be oxidized in aqueous solution, giving in this case methanol as the product (after 20 h at 20 °C, the turnover number equals 250). The reagent also oxygenates arenes to phenols, alcohols to ketones and hydroperoxidizes the allylic position in olefins.

The crucial step of the oxidation by the ‘O₂–H₂O₂–VO₃^––pyrazine-2-carboxylic acid’ reagent is the very efficient generation of HO^• radicals. These radicals abstract hydrogen atoms from the alkane, RH, to generate the alkyl radicals, R^•. The latter react rapidly with an O₂ molecule affording the peroxo radicals, ROO^•, which is then transformed simultaneously into three products: alkyl hydroperoxide, ketone, and alcohol. The proposed mechanism (Fig. 3) of HO^• generation involves the reduction of V(V) species 13 by the first molecule of H₂O₂ to give V(IV) derivative 16. No oxidation occurs in the absence of pyrazine-2-carboxylic acid. The possible role of pyrazine-2-carboxylic acid is its participation (in the form of a ligand at vanadium centre) in the proton transfer, which gives the hydroperoxy derivative of vanadium. One can assume that the nitrogen atom of this ligand is de-coordinated and then abstracts a proton from the coordinated hydrogen peroxide molecule. As a result, a pyridinium base is formed, which, after rotation of the ‘robot’s arm’, approaches one of the =O ligands at vanadium and protonates it to give the –OH ligand (Fig. 4).

Alkanes can be oxidized by hydrogen peroxide in acetonitrile using tetra-n-butylammonium salts of the vanadium-containing polyphosphomolybdate [PMo₁₁VO₄₀]^4– as catalyst [84]. The oxidation of alkanes gives rise to the corresponding alkyl hydroperoxides as the main products, which slowly decompose in the course of the reaction to produce the corresponding ketones (aldehydes) and alcohols. The total yield of the reaction products in the presence of pyrazine-2-carboxylic acid is almost unchanged; however, the initial reaction rate is higher in this case.

5.2 The ‘[L₂Mn₂O₃](PF₆)₂ (L = 1,4,7-trimethyl-1,4,7-triazacyclononane)-carboxylic acid’ system

We have demonstrated that manganese (IV) derivative [L₂Mn₂O₃](PF₆)₂ (21) (L = 1,4,7-trimethyl-1,4-7-triazacyclononane) (Fig. 5) catalyses very efficiently the oxygenation of various organic compounds in acetonitrile or nitromethane, only if a carboxylic acid is present in small concentrations in the reaction mixture [85–90]. Higher (n-hexane and n-heptane, decalin, cyclohexane, methylcyclohexane etc.) and light (methane, ethane, propane, normal butane and isobutane) alkanes can be easily oxidized by this system at room temperature, at 0 °C and even at –22 °C. Turnover numbers of 3300 have been attained and the yield of oxygenated products is 46%, based on the alkane. The oxidation initially affords the corresponding alkyl hydroperoxide as the predominant product; however, this compound decomposes later on, to produce the corresponding ketone and alcohol.

Regio- and bond-selectivities of the reaction are high: C(1):C(2):C(3):C(4) ≈ 1:40:35:35 and 1°:2°:3° is 1:(15–40):(180–300). The reaction with cis- or trans-isomers of decalin gives (after treatment with PPh₃) alcohols hydroxylated in the tertiary position with a cis/trans ratio of ~2 in the case of cis-decalin, and with a trans/cis ratio of ~30 in the case of trans-decalin. It has been proposed [89] that the catalytically active compound 24 is formed in the solution (Fig. 6). The alkane oxidation in the oxidase cycle begins with hydrogen-atom abstraction from the alkane by an oxygen-centred radical or a radical-like species 28 (Fig. 7). The active oxidant is probably a dinuclear manganese complex (HOO–)MnMn(=O), and the reaction occurs via an ‘oxygen-rebound mechanism’ between radical R^• and HOO- group, to produce ROOH with retention of stereochemistry (step 10). Alkyl radicals (R^•) can also partially escape from the solvent cage and react with dioxygen to generate ROO^• and subsequently ROOH, with some loss of stereochemistry. Species 24 also simultaneously catalyses the ‘non-productive’ H₂O₂ decomposition to O₂ and H₂O in the catalase cycle (Fig. 7).

Soluble manganese (IV) complex containing as ligands 1,4,7-triazacyclononane moieties bound to a polymeric chain (compound 32, Fig. 8) catalyses [90] the oxidation of alkanes by hydrogen peroxide in acetonitrile at room and lower temperatures. Corresponding alkyl hydroperoxides are the main products. The presence of relatively small amount of acetic acid is obligatory for this reaction. The oxidation of alkanes and olefins exhibits some features (kinetic isotope effect, bond selectivities) that distinguish this system from an analogous system based on dinuclear Mn(IV) complex 21.

The ‘H₂O₂–compound 21–MeCO₂H’ system also [88] transforms secondary alcohols into the corresponding ketones with quantitative yields at room temperature within a few minutes; the yields of aldehydes and carboxylic acids in the oxidation of primary alcohols are lower. Terminal aliphatic olefins such as hexene-1 are quantitatively epoxidized by the same system in acetonitrile at room temperature within 20 min, while the epoxide yield in the analogous reaction with styrene attains only 60% under the same conditions. Finally, dimethylsulfide can be quantitatively and selectively converted into dimethylsulfoxide within 3 h at room temperature.

5.3 Hydrogen peroxide oxidations catalysed by other metal complexes

5.3.4 Biomimetic oxidations with participation of dinuclear iron complexes

Various dinuclear iron complexes have been synthesized as structural models of diiron non-heme enzymes and their properties were studied. In some cases, activity of such complexes in saturated and aromatic hydrocarbon oxygenations was reported. We have found [99] that, when used in relatively low concentration, compound 33 (Fig. 9) does not catalyse cyclohexane oxidation with H₂O₂ in acetonitrile at room temperature. However, when certain amino acids (pyrazine-2-carboxylic or pyrazine-2,3-dicarboxylic acid) are added in low concentration, efficient cyclohexane oxygenation can be noticed. For the case of pyrazine-2-carboxylic acid, TON = 140. The efficiency of pyrazine-2,3-dicarboxylic acid as co-catalyst is somewhat lower under exactly the same conditions.

The cyclohexane oxygenation reaction is of a first order with respect to both hydrogen peroxide and alkane concentration, since the initial rate of the reaction is proportional to [H₂O₂]₀ and [cyclohexane]₀, respectively. Ethane was transformed by this system mainly to ethyl hydroperoxide as well as to acetaldehyde, in a minor amount. Acetic acid in a very small concentration was detected after 6 h. After this time, the concentrations of ethyl hydroperoxide and acetaldehyde corresponded to TON = 21. Methane was oxidized at 25 °C to produce, after 6 h, methyl hydroperoxide and formaldehyde with TON = 4.

The first step of the process is the reduction of one Fe^III ions with a hydrogen peroxide molecule to produce hydroperoxy radicals and Fe^II. The interaction of Fe^II with H₂O₂ possibly begins from the formation of hydroperoxy derivative. It was assumed that amino acids added to the reaction mixture play a very important role in this stage, facilitating the proton transfer between the coordinated H₂O₂ molecule and ligands at iron centres. Hydroxyl radical attacks an alkane molecule and the alkyl radical thus formed adds rapidly an oxygen molecule affording the corresponding alkyl peroxy radical. This radical can be reduced by one of the two iron(II) centres in a dinuclear complex and, after addition of a proton, a molecule of the alkyl hydroperoxide is formed.

Very recently, we found [100] that hydrogen peroxide oxidizes alkanes in acetonitrile at room temperature if dinuclear iron complex with 1,4,7-triazacyclononane (TACN), compound 34 (which is a model for O₂-transporting proteins hemerythrins), is used as a catalyst (Fig. 10). Pyrazine-2-carboxylic acid accelerates the oxidation [100].