Oxidation of benzyl halides

Ph,P)4Pd(0) and quaternary ammonium salts catalyse the oxidation of benzylic halides by nitrous oxide in a basic medium into O-benzylic ethers of the corresponding aryl aldoximes, ArCH=NOCH2Ar (20-40%) [21 ]. The procedure does not have a great synthetic appeal. 

The oxidation of benzylic halides to aromatic aldehydes and ketones is very easy and is accomplished by many reagents. Very simple ways to prepare aromatic aldehydes from benzyl chlorides and bromides are treat-... 

The Sommelet reaction, also known as the Sommelet oxidation, is the oxidation of benzyl halides (1) to the corresponding aldehydes (3) using hexamethylenetetramine (HMTA) followed by hydrolysis of the hexaminium salt 2.1-3 This reaction is closely related to the Delepine amine synthesis, the Duff aldehyde synthesis, and the Krtihnke reaction (see Section 7.10.3). 

The third variation of the Sommelet reaction is the oxidation of benzyl halide 1 to the corresponding benzaldehyde 3 using 19, the sodium salt of 2-nitropropane (20).18,19... 

Karodia et al. reported [123] a eonvenient method for the acid-catalyzed Michael addition reactions of alcohols, thiols, and amines to methyl vinyl ketone, using the IL ethyltri- -butylphosphonium tosylate. Recently, phosphonium-based ILs have been used [124] in the degradation of phenol, esterification, Wittig reaction, Heck reactions, Suzuki cross-coupling reactions, oxidation of benzyl halides [125], etc. Phos-phonium tosylates are used as solvents in catalytic hydroformy lation reactions these catalyst systems are noncorrosive and can readily be recovered and reused [126]. 

Mild and selective oxidation of aryl halides to corresponding aldeliydes using iodoxybenzoic acid as oxidizing agent and IL has been reported [145]. An efficient oxidation of benzyl halide was reported [146] using aqueous hydrogen peroxide (30%) in trihexyl(tetradecyl)phosphonium-tetrafluroborate IL the protocol is simple and mild offering excellent yield of product. 

Nucleophilic substitution of the halogen atom of halogenomethylisoxazoles proceeds readily this reaction does not differ essentially from that of benzyl halides. One should note the successful hydrolysis of 4-chloromethyl- and 4-(chlorobenzyl)-isoxazoles by freshly precipitated lead oxide, a reagent seldom used in organic chemistry. Other halides, ethers, and esters of the isoxazole series have been obtained from 3- and 4-halogenomethylisoxazoles, and 3-chloro-methylisoxazole has been reported in the Arbuzov rearrangement. Panizzi has used dichloromethylisoxazole derivatives to synthesize isoxazole-3- and isoxazole-5-aldehydes/ ... 

The development of the Grignard-type addition to carbonyl compounds mediated by transition metals would be of interest as the compatibility with a variety of functionality would be expected under the reaction conditions employed. One example has been reported on the addition of allyl halides to aldehydes in the presence of cobalt or nickel metal however, yields were low (up to 22%). Benzylic nickel halides prepared in situ by the oxidative addition of benzyl halides to metallic nickel were found to add to benzil and give the corresponding 3-hydroxyketones in high yields(46). The reaction appears to be quite general and will tolerate a wide range of functionality. 

The traditional oxidation of benzylic and other halides to the aldehyde using DMSO (Kornblum oxidation) has been known for about 35 vears246,362,363. Modified oxidations of this type using selenoxides364,365 and 2-nitropropane366,367 have proved more versatile since other functional groups that are sensitive to the traditional oxidation procedure may be tolerated. In the reaction with 2-nitropropane, allylic halides are readily converted into aldehydes with retention of the alkene geometry. 

Caldarelli et al. (240) have recently reported a five-step synthesis of substituted p)Trole libraries L22 and L23 using solid-supported reagents and scavengers. The synthesis involved oxidation of benzyl alcohols Mi to aldehydes (step a, Fig. 8.46), Henry reaction of aldehydes 8.91 with nitroalkanes M2 (step b), and acylation and elimination of nitroalcohols 8.93 (steps c and d) to give the nitrostyrenes 8.94, which were subjected to 1,3-dipolar cycloaddition with an isocyanoacetate (step e) to give the pyrroles 8.95. N-alkylation of these pyrroles with alkyl halides (step f) and final library-from-a-library hydrolysis/decarboxylation of L22 gave a library of trisub-stituted pyrroles L23 (step g. Fig. 8.46). 

Representative examples of the reaction are shown in equations (16)-(20). The method works well for i iinaiy allylic and benzylic chlorides and bromides, lliere appear to be no examples of the oxidation of secondf halides to ketones by this method, presumably for reasons of lower reactivity. Neither are there any reports of the oxidation of anyl compounds, which is curious since these would be expected to be good substrates. 

For the sake of completeness, examples of benzylic halide oxidation with copper(II) nitrate ° and lead(Il) nitrate are shown in equations (46) and (47). It is probable that the more modem methods would give better yields. 

Oxidation of alkyl halides. This reagent oxidizes benzyl and allyl halides to the corresponding carbonyl compounds in high yield. Secondary alkyl bromides afiord ketones in good yield, but primary alkyl bromides are oxidized in low yield to aldehydes. ... 

Sodium hypochlorite is used for the epoxidation of double bonds [659, 691] for the oxidation of primary alcohols to aldehydes [692], of secondary alcohols to ketones [693], and of primary amines to carbonyl compounds [692] for the conversion of benzylic halides into acids or ketones [690] for the oxidation of aromatic rings to quinones [694] and of sulfides to sulfones [695] and, especially, for the degradation of methyl ketones to carboxylic acids with one less carbon atom [655, 696, 697, 695, 699] and of a-amino acids to aldehydes with one less carbon [700]. Sodium hypochlorite is also used for the reoxidation of low-valence ruthenium compounds to ruthenium tetroxide in oxidations by ruthenium trichloride [701]. 

Related to these reactions is the oxidation of alkyl halides or tosylates to carbonyl compounds with dimethyl sulfoxide (or trimethylammonium A/-oxide). The reaction is effected simply by warming the halide (normally the iodide) or sulfonate in DMSO (or MeaNO), generally in the presence of a proton acceptor such as sodium hydrogen carbonate or a tertiary amine. Oxidation never proceeds beyond the carbonyl stage and other functional groups are unaffected. The reaction has been applied to benzyl halides, phenacyl halides, primary sulfonates and iodides and a limited number of secondary sulfonates. With substrates containing a secondary rather than primary halide or sulfonate elimination becomes an important side reaction and the oxidation is less useful with such compounds. 

A unique method of oxidation of primary and secondary alcohols was found by Tamaru, who reported that the Pd-catalyzed oxidation of alcohols with aryl halides proceeds under basic conditions involving /3-H elimination of the alkoxypalladium 1 [1]. Guram et al. reported that cheaply available chlorobenzene can be used for the oxidation of benzyl alcohols and some secondary aliphatic alcohols in toluene at 105 °C using biphenylyl(dicyclohexyl)phosphine (IV-2) as a ligand. Sterically hindered aliphatic alcohol was oxidized using /-BuONa as a base [la]. 

The reactions of benzylic halides with carbon monoxide and alcohols form esters in good yields. However, the reactions of alkyl halides are more limited for two reasons. First, the oxidative addition of alkyl halides occurs less readily to palladium complexes than the oxidative addition of aryl halides. This difference was noted in Chapter 7. Second, the intermediate alkylpalladium halide can undergo P-hydrogen elimination. As noted in Chapters 9 and 10, these hurdles have been overcome in some cases, and cross-coupling... 

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