Aromatics, acetoxylation

As an example, it has been suggested 37-) that many anodic substitution reactions of aromatic hydrocarbons are ECEC processes, as shown below for anodic aromatic acetoxylation Eqs. (2-5) ) ... 

In 2009, we suggested that Pd-catalyzed aromatic C-H acetoxylation may proceed via dinuclear Pd(III) complexes instead of via mononuclear Pd(IV) intermediates [109]. On the basis of dinuclear Pd(II) complex 36, the product of cyclometallation of 2-phenylpyridine (48) with Pd(OAc)2 [110], a synthesis cycle based on dinuclear Pd(III) complexes was established (Fig. 28). Oxidation of 36 with PhI(OAc)2, a common oxidant in Pd-catalyzed aromatic acetoxylation, afforded dinuclear Pd(III) complex 50. Complex 50 was observed to undergo C-O reductive elimination under pseudocatalytic conditions to generate 49 in 91% yield. The critical dinuclear Pd(III) intermediate (50) was crystallographically characterized the Pd-Pd distance in 50 was measured to be 2.555 A (compared with 2.872 A for 36 [111]), consistent with the formation of a Pd-Pd single bond. Dinuclear Pd(III) complex 50 was found to be a kinetically competent catalyst in the acetoxylation of 2-phenylpyridine with PhI(OAc)2. 

The addition of sulphuric acid increased the rate of nitration of benzene, and under the influence of this additive the rate became proportional to the first powers of the concentrations of aromatic, acetyl nitrate and sulphuric acid. Sulphuric acid markedly catalysed the zeroth-order nitration and acetoxylation of o-xylene without affecting the kinetic form of the reaction. ... 

Expts. 16, //. Pure nitric acid was used. In expt. 16 the reaction was of the first order in the concentration of the aromatic, and of half-life 1-1-5 minutes (similar to that of toluene under the same conditions). In expt. 17 the sodium nitrate slowed the reaction (half-life c. 60 min). About 2 % of an acetoxylated product was formed (table 5-4). 

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

More information has appeared concerning the nature of the side reactions, such as acetoxylation, which occur when certain methylated aromatic hydrocarbons are treated with mixtures prepared from nitric acid and acetic anhydride. Blackstock, Fischer, Richards, Vaughan and Wright have provided excellent evidence in support of a suggested ( 5.3.5) addition-elimination route towards 3,4-dimethylphenyl acetate in the reaction of o-xylene. Two intermediates were isolated, both of which gave rise to 3,4-dimethylphenyl acetate in aqueous acidic media and when subjected to vapour phase chromatography. One was positively identified, by ultraviolet, infra-red, n.m.r., and mass spectrometric studies, as the compound (l). The other was less stable and less well identified, but could be (ll). 

Three oxidative reactions of benzene with Pd(OAc)2 via reactive rr-aryl-Pd complexes are known. The insertion of alkenes and elimination afford arylalk-enes. The oxidative functionalization of alkenes with aromatics is treated in Section 2.8. Two other reactions, oxidative homocoupling[324,325] and the acetoxylation[326], are treated in this section. The palladation of aromatic compounds is possible only with Pd(OAc)2. No reaction takes place with PdCl2. 

The constancy of the acetoxylation nitration ratio and zeroth reaction order in aromatic suggested that both reactions were brought about by a common species (protonated acetyl nitrate) the formation of which was rate-determining according to equilibria (30) and (31), with the latter being a slow step. Since the total rate of acetoxylation plus nitration is given by... 

Aromatic compounds can be hydroxylated, benzoxylated and acetoxylated and the isomer distributions and substituent effects indicate that the reaction is an electrophilic substitution132. Very little kinetic work has been carried out so that the nature of the electrophile is in some doubt. 

Acetoxylation is found to accompany nitration of fairly reactive aromatics by nitric acid in acetic anhydride and gives rise to zeroth-order kinetics76. The electrophile is believed to be protonated acetyl nitrate the formation of which is rate-determining, hence the kinetic order (see p. 37). Acetoxylation can also accompany halogenation by positive halogenating agents in acetic acid solvent, especially in the presence of sodium acetate137, but no kinetic studies have been carried out. 

Similar acetoxylations have been reported for several other aromatic ethers, amines and polynuclear hydrocarbons and more complex reaction products have also been identified, although kinetic data are lacking. 

In the oxidation of aromatic substances at the anode, radical cations or dications are formed as intermediates and subsequently react with the solvent or with anions of the base electrolyte. For example, depending on the conditions, 1,4-dimethoxybenzene is cyanized after the substitution of one methoxy group, methoxylated after addition of two methoxy groups or acetoxylated after substitution of one hydrogen on the aromatic ring, as shown in Fig. 5.55, where the solvent is indicated over the arrow and the base electrolyte and electrode under the arrow for each reaction HAc denotes acetic acid. 

Since these methoxylated and acetoxylated sulfides have an acetal structure, it is expected that Lewis acid catalyzed demethoxylation should generate a carbocation intermediate which is stabilized by the neighboring sulfur atom. In fact, nucleophilic substitution with arenes has been successfully achieved as shown in Scheme 6.7 [43], This procedure is useful for the preparation of trifluoroethyl aromatics. As already mentioned, generation of carbocations bearing an a-trifluoromethyl group is difficult due to the strong electron-withdrawing effect. Therefore, this carbon-carbon bond formation reaction is remarkable from both mechanistic and synthetic aspects. 

BASF has developed a direct electrochemical process based on anodic acetoxylation for the production of aromatic aldehydes on industrial scale [40,146,147]. The reaction passes smoothly through the benzyl acetate stage. 

The anode acetoxylation of aromatic compounds in solutions of acetic acid carrying alkali or tetraalkylammonium acetates takes the same route. As shown (Eberson 1967, Eberson and Jonsson 1981), the process starts with one-electron oxidation at the anode and then passes through the same stages as in oxidation with cobalt trifluoroacetate. The reaction takes place at potentials sufficient to oxidize the substrate but not sufficient to convert acetate ion into acetoxy radical. 

Side-chain acetoxylations of alkyl aromatic compounds can be performed selectively by use of internally electrogenerated cobalt(ni) acetate (Eq. (17))... 

Highly selective formation of phenyl acetate was observed in the oxidation of benzene with palladium promoted by heteropoly acids.694 Lead tatraacetate, in contrast, usually produces acetoxylated aromatics in low yields due to side reac-tions. Electrochemical acetoxylation of benzene and its derivatives and alkoxylation of polycyclic aromatics789 790 are also possible. Thermal or photochemical decomposition of diacyl peroxides, when carried out in the presence of polycyclic aromatic compounds, results in ring acyloxylation.688 The less reactive... 

Several studies have been reported about Pd(II)-cataIyzed acetoxylation. Pd(OAc)2, which catalyzes aromatic coupling and nuclear acyloxylation as well (see Section 9.4.1), is an efficient catalyst of benzylic acetoxylation in the presence of alkali acetates. Stoichiometric oxidation in the absence of oxygen857,858 and a catalytic method858 are known. A twofold rate increase was observed when a mixture of Pd(OAc)2, Sn(OAc)2, and charcoal was employed in acetoxylation.859 Xylenes are converted to the a,a -diacetyloxy compounds in high yields.860... 

Anodic aromatic nuclear substitution is performed to introduce a hydroxy function leading to phenolic compounds. In the first step, acetoxylation or trifluoroacetoxylation occurs usually at carbon electrodes using the acid as solvent [5] ... 

A typical example is the nuclear acetoxylation of an aromatic compound [23] ... 

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