Mechanism acetoxylations

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... 

An especially interesting case of oxygen addition to quinonoid systems involves acidic treatment with acetic anhydride, which produces both addition and esterification (eq. 3). This Thiele-Winter acetoxylation has been used extensively for synthesis, stmcture proof, isolation, and purification (54). The kinetics and mechanism of acetoxylation have been described (55). Although the acetyhum ion is an electrophile, extensive studies of electronic effects show a definite relationship to nucleophilic addition chemistry (56). 

An alternative to the above mechanism is that acetoxylation is an addition-elimination process involving N02 and OAc , leading to nitro and acetoxy products77, and it follows that this process would be less likely to occur, for example, with mesitylene and significantly perhaps, experiments seeking acetoxylation in mesitylene have failed78 on the other hand, mesitylene is a very reactive substrate so it could be that an alternative nitrating species is involved here. 

Further, if the addition-elimination mechanism is correct, then one should observe acetoxylation by nitric acid in acetic acid none has been reported. 

When the initial compound was irani-stilbene, the nnconsnmmated part was recovered with no change in configuration. When di-stilbene was employed as the initial reactant, the recovered olefin was a mixtnre of trans and cis isomers. Hence, the trans confignration is more favorable for oxidative acetoxylation than the cis confignration. In accordance with this conclnsion, the mechanism shown in Scheme 2.30 is proposed. 

According to Ando et al. (2000), the sonolytic acetoxylation of styrene by lead tetraacetate follows the ion-radical mechanism. Lead tetraacetate was not subject to the sonication influence. The ultrasonic effect facilitates electron transfer from styrene (the nonmetallic donor) to lead tetraacetate. 

The proposed mechanism for allyhc acetoxylation of cyclohexene is illustrated in Scheme 15. Pd -mediated activation of the allyhc C - H bond generates a Jt-allyl Pd intermediate. Coordination of BQ to the Pd center promotes nucleophilic attack by acetate on the coordinated allyl ligand, which yields cyclohexenyl acetate and a Pd -BQ complex. The latter species reacts with two equivalents of acetic acid to complete the cycle, forming Pd(OAc)2 and hydroquinone. The HQ product can be recycled to BQ if a suitable CO catalyst and/or stoichiometric oxidant are present in the reaction. This mechanism reveals that BQ is more than a reoxidant for the Pd catalyst. Mechanistic studies reveal that BQ is required to promote nucleophilic attack on the Jt-allyl fragment [25,204-206]. 

Scheme 15 Proposed mechanism for the allylic acetoxylation of cyclohexene...

A widely accepted mechanism for acetoxylation of ethylene is shown in equation (161) and consists of the nucleophilic attack of the acetate anion on the coordinated ethylene, followed by acetoxypalladation and /3-hydride elimination, giving vinyl acetate and palladium hydride.367... 

Nitration is widely applicable, can be carried out under a variety of conditions, can usually be stopped cleanly after mononitration, is usually effected by the nitronium ion, can take place on a neutral molecule or a cation, and in many cases can be considered as the standard aromatic electrophilic substitution. However, this last point must be treated with caution. Depending on the reaction conditions and reagents, the mechanism of the reaction does vary, and accompanying reactions such as oxidation (due to the oxidative action of nitric acid), acetoxylation (by acetyl nitrate), and migration of nitro groups following ipso attack (80MI1) can occur. Ipso nitration processes have been extensively studied by Fischer and co-workers. 

The mechanism of the halogenation is not clearly understood, but it is of interest that the same two bromo compounds were obtained from myoinositol, scyllo-inositol, or the active inositols. Presumably, participation by neighboring acetoxyl groups takes place and a common intermediate is involved. epf-Inositol gives mainly one monobromo compound, of unknown configuration.242... 

The reaction of C 4-acetoxylated catechin 517 and epicatechin with nucleophiles under Lewis acid conditions to yield C-4-elaborated flavan-3-ols 518 has been described. The C 4 acetoxy group is activated by a Lewis acid, such as BFj-OEo or TMSOTf, allowing delivery of a variety of carbon-, nitrogen-, and sulfur-based nucleophiles in stereoselective fashion to this position (Scheme 94) <2002TL7753>. An SnI mechanism was invoked for the process. Table 4 displays the results for catechins. 

Anodic acetoxylation is an illustrative example of these principles. Anodic oxidation of sodium acetate in acetic acid at a platinum anode under constant current conditions yields ethane in almost quantitative yield. The mechanism was supposed to be discharge of acetate ion at the anode with formation of an acetoxy radical, which subsequently would undergo decarboxylation with formation of methyl radicals as shown in Eqs. (14) and (15). 

Another approach to the problem involves the study of molecules in which one side is more accessible for adsorption than the other one. This feature is to a certain extent present in 2-t-butylindane which would be predicted to form substrate-electrode complex 15 preferentially. On anodic acetoxylation of 2-t-butyl-indane a mixture of cis- and r/vz s-l-acetoxy-2-t-butylindane in the proportions 16 84 is formed 106 Vhi all probability via a carbonium ion mechanism (Eq. 

Side-chain substitution of aromatics is best rationalized by an ECrECn me" chanism via a radical cation 30 in Eq. (101) as intermediate 106-226-241-243. Yet side products of typical radical origin, e.g., bibenzyl in acetoxylation of toluene, have been accounted in favor of a radical chain mechanism (Eq.(99) ) 230, 244,24 5) An ECE-mechanism however has been clearly demonstrated by cyclic voltammetry for side-chain substitution of pentamethylanisole and p-methoxy-toluene 241 Eberson has proposed a modified ECrECn mechanism to account for the formation of radical coupling products 242 (Eq. (101) ) The radical cation 30, the first intermediate, can escape from the electrode surface and loose a proton to form a benzyl radical in the bulk of the solution. This benzyl radical can couple to bibenzyl or abstract hydrogen to form starting material. 

If Stern s and Eberson s mechanisms are combined, the following tentative scheme can be formulated for competing nuclear acetoxylation, side-chain acetoxylation, and oxidative coupling in Pd(II) oxidations of alkylbenzenes (initial attack is shown only for the para position a similar scheme can be written with initial attack at the ortho position) ... 

Investigation of the use of acetyl hypofluorite in acetic acid for the regiocontrolled monofluorination of aromatic compounds starting from the corresponding mercurated derivatives has been carried out by Visser and coworkers29 (equation 19). On the basis of the observed fluorinated (7), acetoxylated (8) and methylated (9) products, a one-electron-transfer mechanism leading to an intermediate radical cation was proposed which might... 

Aryllead(rv) triacetates react with phenols to give mainly products of ortho-C-arylation, formed by ligand coupling mechanisms.45 4511 65 In an attempt to extend the arylation of polymethylbenzenes to phenolic substrates, Pinhey et al. treated mesitol 30 with /(-rncthoxy phenyl lead triacetate 1 in CHCI3 (Equation (37)). The reaction afforded a mixture of the C-arylated products 31 and 32 together with minor amounts of the C-acetoxylated product 33 and O-aryl ether 34.45 45a... 

A particular use of aryllead triacetate is reported74 by which cycloalkanone enamines are arylated at the /f-carbon atom, giving sometimes acetoxylated compounds as by-products, by a mechanism analogous to that proposed for thallium triacetate75. 

The kinetics and the mechanism of the gas phase acetoxylation of ethylene on palladium catalyst has been the subject of many studies. These studies are based on a Langmuir-Hinshelwood type mechanism in which all reacting species are chemisorbed on the Pd surface and reaction occurs between chemisorbed species. Although a complete description is still pending a commonly accepted proposal is shown in Figure 30. 

Figure 30 Mechanism of the acetoxylation of ethylene in the gas phase process.

Other transition metal salts mediate in similar oxidations. For example, mercury(II) acetate, a milder reagent than LTA, effects a-acetoxylation through a comparable mechanism. However the corresponding yields for these processes are poor. 3,3-Dimethylcyclohexanone, for example, is oxidized to the a-acetoxy derivative in only 14% yield.The, 7-unsaturated ketone, isopugelone, exhibits no oxidation at the a- or a -positions, but affords a product derived from isomerization of the alkene and allylic oxidation. Not surprisingly therefore the reagent has found little synthetic application for this transformation. 

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