Substituted Benzyl Acetates

Direct esr evidence for the intermediacy of radical-cations was obtained on flowing solutions of Co(III) acetate and a variety of substituted benzenes and polynuclear aromatics together in glacial acetic acid or trifluoroacetic acid solution . A p value of —2.4 was reported for a series of toluenes but addition of chloride ions, which greatly accelerated the reaction rate, resulted in p falling to —1.35. Only trace quantities of -CH2OAC adducts were obtained and benzyl acetate is the chief product from toluene, in conformity with the equation given above. 

The isomer distribution obtained from the oxidation of mesitylene in acetic acid, sodium acetate depends on the anode material. Graphite strongly favours nuclear substitution to side chain substitution in the ratio 23 1 while at platinum this ratio is 4 1. Oxidation of methyl benzenes in acetic acid containing tetrabutykmmonium fluoroborate and no acetate ion gives benzyl acetate as the major product since loss of a proton from the radical-cation is now faster than nuclear substitution by acetic acid as the only nucleophile present [39]. 

On the basis of this pioneering work, Rubenbauer and Bach developed a Bi(OTf)3-catalyzed highly diastereoselective benzylation of silyl enol ethers [65]. Various cyclic and acyclic silyl enol ethers were amenable to this protocol (Scheme 24). Various a-substituted benzyl acetates were tested with terf-butyl-substituted silyl enol ether 31a, and the use of only 1 mol% of Bi(OTf)3 was enough to obtain the desired benzylated ketones 32 in high yields and with excellent diastereoselectivities (up to 95 5). Whereas a-nitro- (30a), ot-cyano- (30b) and a-methylester-substituted (30d) benzyl acetates gave the anti diastereoisomer as the major product, the phosphonate-substituted benzyl acetate (30c) exclusively resulted in the syn isomer (Scheme 24). 

Oxidation with peroxydisulfate in AcOH in the presence of catalytic amounts of iron and copper salts gives benzylic acetates in good yields.785,861 The reaction of lead tetraacetate with alkylarenes in AcOH provides benzylacetates in moderate yields.693 Most of these oxidations usually involve methyl-substituted benzenes since aromatics with longer chain produce different side products. 

Hilborn, J.W., MacKnight, E., Pincock, J. A. and Wedge, P.J. (1994) Photochemistry of substituted benzyl acetates and benzyl pivalates a reinvestigation of substituent effects. Journal of the American Chemical Society, 116, 3337-3346. 

A particularly illuminating study involving isotopic substitution concerns the reaction of N-tritiated diethylamine with methyl benzoate (Kitamura et al., 1977). It was found that tritium was preferentially substituted into the p-position. There was also substantial substitution in the o-position but more surprising, the methyl group of the ester was labelled. It was proposed that reaction occurs as shown in Scheme 7 via radical ions [68] and [69]. 4-Cyano-benzyl-acetate, on irradiation in the presence of triethylamine is cleaved to give 4-cyanotoluene and 4,4 -dicyanobibenzyl (Ohashi et al., 1977d). When O-deuteriated methanol was used as solvent, deuterium was incorporated... 

Toluene was oxidized to a mixture of benzyl acetate (31) and benzylidene diacetate (32) on reaction with oxygen in the presence of a silica supported Pd-Sn catalyst.A reaction run in HOAc/KOAc at 70°C under an atmosphere of oxygen gave a near 3 1 ratio of the monoacetate to the diacetate at 98% conversion (Eqn. 21.40). The two products are formed in parallel reactions as the benzylacetate does not react further under these reaction conditions. Substituted diphenylmethanes were oxidized to the diphenyl ketones by refluxing them in air in a DMF solution containing a copper powder catalyst.""... 

The oxidation of substituted aromatic hydrocarbons by Mn(OAc)3 in refluxing acetic acid proceeds by two competing mechanisms (a) a free radical addition of carboxymethyl radical to the nuclear ring, forming 2-arylacetic acids and (b) a benzylic hydrogen abstraction by Mn resulting in the formation of benzyl acetates. " In the presence of strong acids such as sulfuric, trichloro- or trifluoro-acetic acids, only benzylic oxidation products are readily formed at room temperature (equation 207). ... 

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)). 

Alkyl-substituted benzenes and alkyl-substituted aromatic compounds constitute the starting molecules. Benzaldehydes, benzyl acetates, and to some extent also benzyl alcohols are the main intermediates aromatic carboxylic acids are the desired products. The intermediate benzyl acetates, benzaldehydes, and the corresponding acids can also be formed in stoichiometric reactions with Co(OAc)3 in acetic acid in the absence of oxygen. 

In the rate-determining step the alkyl-substituted aromatic compound reacts reversibly with a Co species via electron transfer to a radical cation which forms the thermodynamically favored benzylic radical by elimination of (see eqs. (2) and (3)). Benzyl acetate is derived from the subsequent reaction of the benzyl radical with cobalt(III) acetate under anaerobic conditions (eq. (5)). 

Metal-mediated approaches to the synthesis of imidazoles have been reported. PaUadium(ll)-catalyzed intermolecular 1,2-diamination of conjugated dienes with ureas led to 4-alk enyl-2-imidazolones in good yields rmder mild conditions <05JA7308>. Palladium-catalyzed cyclization of O-pentafluorobenzoylamidoximes 74 furnished l-benzyl-2-substituted-4-methylimidazoles 75 <050L609>. Direct copper(I)-chloride mediated reaction of nitriles 76 with a-amino acetals 77 followed by acidic reaction led to a variety of 2-substituted imidazoles 78 <05TL8369>. 

Scheme 2 Photolysis of methoxy-substituted benzyl acetates in 80% aqueous dioxane.

Oxidation of the isomeric xylenes by manganese(III) acetate in the absence of O2 gives methyl substituted benzyl acetates by a mechanism similar to the oxidation of toluene. ... 

Nucleophilic substitution. Benzylic acetates react with nucleophiles such as amines, sodium arenesulfonates, and malonic esters under the influence of the title reagent together with DPPF and a mild base [Et3N in EtOH or K2CO3 in t-AmOEl]. 

Other crosslinkers have been also extensively studied (Fig. 123). Benzyl acetate derivatives are such a latent electrophile, which yields a stable benzylic carbocation, releasing acetic acid, upon acid treatment. The carbocation undergoes electrophilic substitution reactions onto the electron-rich benzene ring and crosslinks the phenolic resin when the latent electrophile is multifunctional [366-370]. The crosslinker can be an additive or incorporated into a phe-... 

Scheme 6.13 Chemical amplification mechanism involving acid-catalyzed cross-linking of a benzyl carbocation (from benzyl acetate) and a substituted phenol. Note that in step 1, photolysis of the acid generator produces a latent image of acid, while in step 2, acid-catalyzed thermolysis of the acetate produces a carbocation ion. Step 3 shows the carbocation reacting with an appropriately substituted aromatic compound in an electrophilic substitution reaction that produces a covalent linkage and regenerates the acid. There is no net consumption of acid.

Benzyl acetates. Arylacetic acids undergo oxidative decarboxylation with Mn(OAc)j in HOAc. The intermediate benzyl cations are quenched by HOAc. An electron-donating p-substituent in the aromatic ring and higher a-substitution favor the reaction. 

Two generally accepted reaction mechanisms for benzylic acetoxylation are shown in Scheme 8.8 [79b]. One proceeds with the rupture of a benzylic C-H bond to give surface-bound benzyl and hydride species. The Pd-benzyl species is then attacked by acetate. The other mechanism involves a concerted substitution to add an acetate ion and release of hydride to the Pd surface. This field continues to be an area of active research [85-88, 88], although high yields of benzyl acetate remain elusive [89]. 

Cyclobutylidene derivatives have been regio- and stereoselec-tively reduced to substituted vinyl cyclobutanes with Pd(dba)2 and sodium formate. Heteroaryl benzylic acetates (including 2° acetates) undergo Pd-catalyzed benzylic nucleophilic substitution with malonate nucleophiles. Cyclobutanone O-benzoyloximes have been converted to a variety of nitrile derivatives using Pd(dba)2 in combination with chelating phosphines (eq 27). ... 

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