Acetoxylation, toluene

Tmta — see Acetic acid, trimethylenediaminetetra-Tollen s reagent, 5, 780 Tolman s cone angle, 2, 1015 Toluene acetoxylation... 

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... 

Acetoxylation. Although furans are readily oxidized, furans substituted by a triisopropylsilyl (TIPS) group when treated with DDQ in toluene-acetic acid at 0° undergo acetoxylation at an adjacent a-methylene group.3... 

Alkoxyl and acetoxyl protons in A-acetoxy-A-alkoxybenzamides give rise to sharp signals well below room temperature. In contrast, hydroxamic esters usually exhibit line broadened alkoxyl group resonances in their H NMR spectra at or even signihcantly above room temperature" . In toluene-rfg, the benzylic and acetoxyl methyl resonances of A-acetoxy-A-benzyloxybenzamide (100) showed signihcant line broadening below 250 K but remained isochronous down to 190 K. 

Acetoxylation of toluene using a Pd(OAc)2-Sn(OAc)2-charcoal catalyst selectively produces benzyl acetate with high turnover numbers ( 100).373,434 The active catalyst presumably contains Pd—Sn bonds. Tin ligands are known to increase the 7r-acceptor ability of palladium, and may favor the coordination of the toluene in the form of a benzylic 7r-allyl complex (141) which is nucleophilically attacked by the acetate anion.435... 

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. 

Bryant et al.s96 found that the relative amounts of oxidative coupling and side-chain acetoxylation of toluene are determined by the molar ratio of PdCl2 and acetate present. For molar ratios of NaOAc PdCl2 equal to 5 and 20, the relative yields of bitolyl benzyl acetate were 64 2 and 1 68, respectively. Similarly, in the oxidation of toluene with Pd(OAc)2-KOAc in acetic acid, increasing the molar ratio of KOAc to Pd(OAc)2 from 5 to 20 improved the yield of benzyl acetate from 53 to 93%. 

The cyclic vinyl ether (182),170 postulated last year as an intermediate in the 21-acetoxylation of the hemiacetal (183), can be prepared in good yield by heating the hemiacetal with aluminium isopropoxide in toluene under argon, followed by direct chromatography on basic alumina.171 The vinyl ether was converted into the 20,21-diol (184) either by reaction with osmium tetroxide or by acetoxylation with lead tetra-acetate, followed by hydrolysis. The hypoiodite reaction, followed by oxidation, allows direct conversion of a 21-acetoxypregnan-20/3-ol (185) into the 18-iodo-20-ketone (186), which is solvolysed in the presence of silver acetate to provide a new route to the 21-acetate of 18-hydroxydeoxycorticosterone hemiacetal (187).171... 

In contrast, anodic cyanation of diphenylacetylene occurs exclusively at the aromatic ring and the triple bond remains intact 4-cyanodiphenylacetylenc is formed in 60% yield. The reaction was run at 2 V (vs. S.C.E.) for 3-9 F mol" using a platinum anode in methanol containing sodium cyanide. Anodic cyanation results in preferred attack at the aromatic nucleus in other systems toluene, mesitylene and hexamethylbenzene give nuclear substitution and little side-chain cyanation under similar conditions in contrast with the corresponding acetoxylation or methoxylation reactions. 

Copper acetate, Cu(OCOCHj)2 or Cu(0C0CH3)2 H20, resembles copper sulfate in its oxidizing properties and is used for the oxidative coupling of terminal acetylenes [53, 357] and for the conversion of acyloins into a-diketones [353, 359]. Its presence favorably affects the acetoxylation of toluenes to benzyl acetates by sodium persulfate [360]. 

The outer-sphere OAc anions can be replaced by other anions. For instance, the and PF anions readily substitute for OAc anions in an aqueous solution containing KPFft, affording the giant cluster with the idealized formula [Pdsei LeoOeoKPFeleo [Ik 16, 17]. The Pd-561 clusters exhibit a high catalytic activity in alkene acetoxylation in an AcOH solution under mild conditions (20-60 °C at 0.1 MPa). Besides reaction (1), the clusters provide the oxidative acetoxylation of propylene to allyl acetate (eq. (6)) or of toluene to benzyl acetate (eq. (7)). 

Acetoxylation of aromatics (eq. (25)) was first carried out by Davidson and Triggs [92] to produce phenyl acetate, which could give rise to the development of a new phenol synthesis. The formation of phenyl acetate is accompanied by the formation of biphenyl (see Section 3.3.14.7.2). In the presence of oxidants such as Pb(OAc)4, NaN02, NaNOs, KMn04, K2CrOv [93] and P-Mo-V heteropolyacids [94], phenyl acetate is the main product. The favored ring acetoxylation with high-oxidation-state Pd catalyst over dimerization with low-oxidation-state catalyst has recently been confirmed [95]. With toluene, probably in an allylic-like oxidation, benzyl acetate is obtained [92]. 

Acetoxylation of N-acyl-2,3-dihydro-4-pyndones. Vinylogous amide derivatives such as the dihydropyridones undergo smooth acetoxylation at C-3 (trans to an existing substituent at C-2) with Pb(OAc) in refluxing toluene. The products are useful synthetic intermediates. 

Acetoxylation of hydrocarbons. I n a paper of 1923Dimroth reported preliminary observations on the oxidation of aromatic hydrocarbons and olefins with lead tetraacetate. Toluene, he found, affords benzyl acetate in very low yield oxidation of diphenylmethane and triphenylmethane proceeded more readily but offered nothing of preparative promise. Dimroth observed also that anethole reacts to give in small yield a product of addition of two acetoxyl groups to the olefin linkage. 

Nuclear acetoxylation is the slow step (Andrulis and Dewar, 1966). It has been suggested that the slow step in oxidations of toluene by Co(III) acetate (Heiba et al., 1969b Sakata et al.,... 

In his pioneering contributions Moiseev has shown that giant cationic palladium clusters , e.g. Pd56iL6o(OAc)i8o (L = phenanthroline, bipyridine), characterized by use of high-resolution TEM, SAXS, EXAFS, IR and magnetic susceptibility data, catalyze, under mild conditions (293 363 K, 1 bar), the oxidative acetoxylation of ethylene into vinyl acetate, propylene into allyl acetate, and toluene into benzyl acetate. The oxidation of primary aliphatic alcohols to esters, and the conversion of aldehydes into acetals were also studied. ... 

Benzyl acetates are important precursors to fragrances, and their hydrolyzed alcohol products are valuable synthons. Benzylic acetoxylation of toluene to benzyl acetate is seen as a potential route for commercial production. The major existing route to benzyl acetate proceeds via benzyl chlorides [71]. Pd-catalyzed aerobic acetoxylation toluene and other methyl arenes would offer an appealing alternate route to these products (Scheme 8.7). 

Early observations of benzylic acetoxylation were made in the study of arene acetoxylation and biaryl coupling when toluene was used as a substrate. In 1966, the reaction between stoichiometric Pd(OAc)2 and toluene to give benzyl acetate as the major product was disclosed [72]. Two years later, acetoxylation of toluene with catalytic Pd salts was reported by Union Carbide by using phosphines or a combination of Sn(OAc)2, charcoal, and air as oxidant to give 96TONs [73]. Additional metal acetates such as KOAc are beneficial for the reaction [74]. These acetoxylation methods were further applied to other arenes [75] (e.g., benzene, cyclohexene) and the synthesis of benzyl diacetate [76] (a precursor to benzalde-hyde). 

Scheme 8.8 Proposed mechanism for Pd-based acetoxylation of toluene [79b].

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