Oxidation benzylic halides

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/ ... 

Ag Salt. It is prepd by the action of Ag oxide on TNMe in eth, mp 100° (Ref 3). It reacts with benzyl halides to form trinitroethyl derivs (Ref 17). Explodes mildly on rapid heating (Ref 3)... 

Poly (ethylene oxide) macromonomers72 761 are made in a similar way, as the alkoxide end group is reactive enough towards benzylic halides. With methacryloyl chloride, side reactions are involved. It is better to first protonate the PEO, and then to have it react with methacryloyl chloride in the presence of some triethyl amine. One can also react co-hydroxy polyethylene oxide) with methacryloyl imidazole, or with methacrylic acid in the presence of dicyclohexyl carbodiimide (DCCf)77). 

Aromatic brominations have been mainly carried out using X, Y and L zeolites. Improved para/ortho ratios have been observed upon brominating halobenzenes, benzyl halides, and biphenyl. The side product HBr leads to decreased activity and selectivity. This problem has been addressed by adding scavengers, by working in the gas phase, and by applying oxidative bromination. 

Another reagent that convert benzylic halides to aldehydes is pyridine followed by /7-nitrosodimethylaniline and then water, called the Krohnke reaction. Primary halides and tosylates have been oxidized to aldehydes by trimethylamine N-oxide, and by pyridine N-oxide with microwave irradiation. ... 

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. 

Experimental tests of the theoretical predictions have involved the electrochemical reduction of alkyl and benzyl halides as well as their reduction by homogeneous electron donors.22,29-31 In the first case, AG° = E - rx r.+x=f where E is the electrode potential and rx r.+x=f is the standard potential of the RX/R + XT couple. In the homogeneous case, AG° = E q — rx r-+xt> where E Q is the standard potential of the outer-sphere electron donor or acceptor couple P/Q, and + stands for a reduction and — for an oxidation. 

For example, direct treatment of red phosphorus with potassium hydroxide in a mixture of dioxane and water with a phase-transfer catalyst (benzyltriethylammonium chloride) allows direct reaction with primary haloalkanes to form the trialkylphosphine oxide in moderate (60-65%) yield.1415 Allylic and benzylic halides are similarly reported to generate the corresponding tertiary phosphine oxides. When the reaction is performed with a,(o-dihalides, cyclic products are generated only with four- and five-carbon chains the third site... 

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 results from our work on the reaction of propylene oxide with cobalt carbonyl and base in methanol are given in Table VIII. Several base/metal oxide combinations were evaluated under mild reaction conditions. The difference in activity between the bases was not as pronounced as that observed in the reaction with benzyl halides with the exception of potassium methoxide which, when used alone, gave exclusively the hydroxy ether resulting from methoxide addition to the epoxide ring. However, the activity of sodium... 

The possibility that substitution results from halogen-atom transfer to the nucleophile, thus generating an alkyl radical that could then couple with its reduced or oxidized form, has been mentioned earlier in the reaction of iron(i) and iron(o) porphyrins with aliphatic halides. This mechanism has been extensively investigated in two cases, namely the oxidative addition of various aliphatic and benzylic halides to cobalt(n) and chromiumfn) complexes. 

Finally, the hybridization of the carbon atom also has a marked effect on its willingness to attach to the transition metal. Allyl or benzyl halides undergo oxidative addition faster than aromatic or vinyl halides. The least reactive are alkyl halides which require the use of nickel(O)9 complexes or highly active catalyst systems.10 If we start from an optically active substrate, then the oxidative addition usually proceeds in a stereoselective manner. 

Another way to oxidize primary alkyl halides to aldehydes is by the use of hexamethylenetetramine followed by water. However, this reaction, called the Sommelet reaction. is limited to benzylic halides. The reaction is seldom useful when the R in RCH2CI is alkyl. The first part of the reaction is conversion to the amine ArCH2NH2 (0-44), which can be isolated. Reaction of the amine with excess hexamethylenetetramine gives the aldehyde. It is this last step that is the actual Sommelet reaction, though the entire process can be conducted without isolation of intermediates. Once the amine is formed, it is converted to an imine (ArCH2N=CH2) with formaldehyde liberated from the reagent. The key step then follows transfer of hydrogen from another mole of the arylamine to the imine ... 

Despite our failure to find any supporting spectral evidence, the suspected presence of a-bromo-o-xylene and the absence of o-methyl-benzyl acetate in the oxidation products from o-xylene suggest a solvolysis rate for this benzylic halide lower than for the isomeric methylbenzyl bromides. 

The substitution of allyl and benzyl halides is also catalyzed by quaternary ammonium halides. In fact, the method was discovered with tributylstannyl ethers [15]. The conversion of tributylstannyl ethers to ketones with AMnomosuccinimide is an alternative to the bromine oxidation of stannylenes [12,13]. Again, the disposal of the tin by-product Bt SnX may be a problem in large-scale wotk. It may be fairly efficiently extracted with hexane from a solution of the reaction mixture in acetonitrile. 

Substrates suitable for oxidative conversion into carbonyl compounds are alkenes, primary or secondary alcohols, and benzyl halides. Polystyrene-bound alkenes have been converted into aldehydes (with the loss of one carbon atom) by ozonolysis followed by reductive cleavage of the intermediate ozonide (Entry 1, Table 12.3). 

LiBr has been reported to catalyse the dihydroxylation of alkenes (1) to afford syn-and anh -diols (2/3) with excellent diastereoselectivity, depending on the use of NaKTt (30 mol%) or PhI(OAc)2 (1 equiv.), respectively, as the oxidant.28 The authors claim that oxidation of non-benzylic halides was achieved for the first time to afford the corresponding diols in excellent yields 28 is not really justified as the development of the silver-free Prevost-Woodward dihydroxylation for non-benzylic substrates had... 

The addition of an alkyl halide to the d7 complex [Co(CN)6]3- results in a one-electron oxidation of the metal and proceeds by homolytic abstraction of halogen. For a methyl or benzyl halide, an organocobalt product is formed,... 

---