Benzylic oxidations cerium ammonium nitrate

Table 4-1 compares two different reactions, namely, anode oxidation and oxidation with cerium ammonium nitrate (which are bona fide electron-transfer processes) and bromination by /V-bromosuccinimide in the presence of azobis(iso-butyro)nitrile (which is bona fide hydrogen-atom-transfer process). Both electron-transfer and hydrogen-atom-transfer processes have the benzylic radical as a common intermediate, but positional selectivity is stronger for electron-transfer processes. Another important point is the preference of the 2-positioned methyl group over the 1-positioned group, in terms of selectivity. For 1,2,3-tetramethylbenzene, such a preference reaches values from 16 to 55, and it is over 200 for 5-methoxy-1,2,3-tctramcthylbcnzcnc. 

PMB ethers can be cleaved oxidatively with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)11 in dichloromethane/water tor with cerium ammonium nitrate (CAN) in acetonitrile/water.12 Many other protecting groups such as esters, isopropylidene acetals, benzyl ethers, allyl ethers and f-butyldiphenyl silyl (TBDMS) ethers are stable to these conditions (Scheme 2.4). The cleavage reaction, with DDQ is initiated with a single-... 

Recently it was pointed out [6] that potassium and sodium bromate oxidize arenes in good yields in a 3 2 dioxane-water solution by using cerium ammonium nitrate (CAN) as catalyst. Toluene derivatives are oxidized to ca. 1 1 mixture of benzaldehydes and benzoic acids, while ethylbenzenes are converted to acetophenones. According to the proposed mechanistic scheme, water either influences the polarity of the reaction medium or acts as the reagent, reacting with the intermediate benzylic carbonium ion to give a hydroxy derivative, which is oxidized from either Ce or BrOa ions. 

Cerium(IV) ammonium nitrate (CAN) in acetic acid oxidizes potassium bromide and, consequently, brominates methylbenzenes at a benzylic position with 50-80% yield293. f-Butyl hydroperoxide (TBHP) oxidizes CuBr2 which a-brominates toluenes to benzyl... 

Primary benzylic alcohols (equation 10) can be oxidized in the presence of saturated primary alcohtris using a catalyst derived from ammonium cerium(IV) nitrate supported on charcoal with air as the cooxidant (under these conditions a-hydroxy ketones are oxidized to a-diketones). ... 

Benzaldehydes can be prepared in good yield from benzyl alcohols by means of various oxidants, including dinitrogen tetroxide (for its preparation see Park and Partington412) in chloroform or carbon tetrachloride,413 concentrated nitric acid,414a aqueous hypochlorite,414b or cerium(iv) ammonium nitrate in 50% acetic acid.415... 

Cerium(IV) has been used extensively, and the two most common reagents are ceric ammonium sulfate [Ce(S04)2 2(NH4)2S04 2 H2O] and ceric ammonium nitrate [Ce(NH4)2(N03)6].l 3 Modified cerium reagents such as Ce(OH)302Hl 4 d [(N03)3Ce]3H2l06l - have been used by Firouzabadi et al. or the oxidation of primary alcohols, especially benzylic and allylic alcohols. 

The p-methoxyphenyl group has recently been found suitable for alcohol protection, as the resulting ethers are stable both to acidic and basic conditions and can be cleaved by brief treatment with ceric ammonium nitrate. The same principle can be applied to carboxylic acid protection.Thus, the rather stable benzyl (64) and phenyl (65) esters can be cleaved as indicated by oxidation with DDQ or cerium(IV)(at pH 3) respectively. A recent total synthesis of (+)-Antimycin-A features the use of a... 

N03)j, a newcomer to the arena of oxidants, is useful for the acetoxylation of aromatic side chains in benzylic positions [415, 416] and for the oxidation of methylene or methyl groups that are adjacent to aromatic rings to carbonyl groups [238, 415, 417]. The reagent also oxidizes alcohols to aldehydes [418, 419, 420, 421] and phenols to quinones [422, 423], cleaves vicinal diols to ketones and a-hydroxy ketones to acids [424, 425], and converts diaryl sulfides into sulfoxides [426]. A specialty of ammonium cerium nitrate is the oxidative recovery of carbonyl compounds from their oximes and semicarbazones [422, 427] and of carboxylic acids from their hydrazides [428] under mild conditions. 

Reactions of ammonium hexanitratocerate(IV) with organic substrates other than benzyl alcohol have also been examined, and 1,4-hydroquinone was quantitatively transformed into 1,4-quinone. Anisole and naphthalene can be nitrated. For the cerium-mediated oxidation reactions in ionic liquids, high reaction temperature is beneficial because of the formation of smaller amounts of by-products. 

Oxalic and malonic acids, as well as a-hydroxy acids, easily react with cerium(IV) salts (Sheldon and Kochi, 1968). Simple alkanoic acids are much more resistant to attack by cerium(IV) salts. However, silver(I) salts catalyze the thermal decarboxylation of alkanoic acids by ammonium hexanitratocerate(IV) (Nagori et al., 1981). Cerium(IV) carboxylates can be decomposed by either a thermal or a photochemical reaction (Sheldon and Kochi, 1968). Alkyl radicals are released by the decarboxylation reaction, which yields alkanes, alkenes, esters and carbon dioxide. The oxidation of substituted benzilic acids by cerium(IV) salts affords the corresponding benzilic acids in quantitative yield (scheme 19) (Hanna and Sarac, 1977). Trahanovsky and coworkers reported that phenylacetic acid is decarboxylated by reaction with ammonium hexanitratocerate(IV) in aqueous acetonitrile containing nitric acid (Trahanovsky et al., 1974). The reaction products are benzyl alcohol, benzaldehyde, benzyl nitrate and carbon dioxide. The reaction is also applicable to substituted phenylacetic acids. The decarboxylation is a one-electron process and radicals are formed as intermediates. The rate-determining step is the decomposition of the phenylacetic acid/cerium(IV) complex into a benzyl radical and carbon dioxide. 

Aromatic nitration or nitration in the benzylic position are often side reactions of oxidation reactions with ammonium hexanitratocerate(IV). In fact these unwanted reactions are one of the main drives to develop cerium(IV) reagents other than ammonium hexanitratocerate(IV). However, in some cases ammonium hexanitratocerate(IV) can be turned into a useful nitration reagent. A major parameter that governs the chemoselectivity of CAN is the solvent. 

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